Proposed Changes to the Enzyme List

References:

1.	Graupner, M., Xu, H. and White, R.H. The pyrimidine nucleotide reductase step in riboflavin and F₄₂₀ biosynthesis in archaea proceeds by the eukaryotic route to riboflavin. J. Bacteriol. 184 (2002) 1952–1957. [DOI] [PMID: 11889103]
2.	Chatwell, L., Krojer, T., Fidler, A., Romisch, W., Eisenreich, W., Bacher, A., Huber, R. and Fischer, M. Biosynthesis of riboflavin: structure and properties of 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5′-phosphate reductase of Methanocaldococcus jannaschii. J. Mol. Biol. 359 (2006) 1334–1351. [DOI] [PMID: 16730025]

[EC 1.1.1.302 created 2010, modified 2011]

1.1.1.315

Accepted name:

11-cis-retinol dehydrogenase

Reaction:

11-cis-retinol—[retinal-binding-protein] + NAD⁺ = 11-cis-retinal—[retinol-binding-protein] + NADH + H⁺

For diagram of retinal and derivatives biosynthesis, click here

Glossary:

11-cis-retinal = 11-cis-retinaldehyde

Other name(s):

RDH5 (gene name)

Systematic name:

11-cis-retinol:NAD⁺ oxidoreductase

Comments:

This enzyme, abundant in the retinal pigment epithelium, catalyses the reduction of 11-cis-retinol to 11-cis-retinal [1] while the substrate is bound to the retinal-binding protein [4]. This is a crucial step in the regeneration of 11-cis-retinal, the chromophore of rhodopsin. The enzyme can also accept other cis forms of retinol [2].

Links to other databases:

References:

1.	Simon, A., Hellman, U., Wernstedt, C. and Eriksson, U. The retinal pigment epithelial-specific 11-cis retinol dehydrogenase belongs to the family of short chain alcohol dehydrogenases. J. Biol. Chem. 270 (1995) 1107–1112. [DOI] [PMID: 7836368]
2.	Wang, J., Chai, X., Eriksson, U. and Napoli, J.L. Activity of human 11-cis-retinol dehydrogenase (Rdh5) with steroids and retinoids and expression of its mRNA in extra-ocular human tissue. Biochem. J. 338 (1999) 23–27. [PMID: 9931293]
3.	Liden, M., Romert, A., Tryggvason, K., Persson, B. and Eriksson, U. Biochemical defects in 11-cis-retinol dehydrogenase mutants associated with fundus albipunctatus. J. Biol. Chem. 276 (2001) 49251–49257. [DOI] [PMID: 11675386]
4.	Wu, Z., Yang, Y., Shaw, N., Bhattacharya, S., Yan, L., West, K., Roth, K., Noy, N., Qin, J. and Crabb, J.W. Mapping the ligand binding pocket in the cellular retinaldehyde binding protein. J. Biol. Chem. 278 (2003) 12390–12396. [DOI] [PMID: 12536149]

[EC 1.1.1.315 created 2011]

1.1.1.316

Accepted name:

L-galactose 1-dehydrogenase

Reaction:

L-galactose + NAD⁺ = L-galactono-1,4-lactone + NADH + H⁺

Other name(s):

L-GalDH; L-galactose dehydrogenase

Systematic name:

L-galactose:NAD⁺ 1-oxidoreductase

Comments:

The enzyme catalyses a step in the ascorbate biosynthesis in higher plants (Smirnoff-Wheeler pathway). The activity with NADP⁺ is less than 10% of the activity with NAD⁺.

Links to other databases:

References:

1.	Mieda, T., Yabuta, Y., Rapolu, M., Motoki, T., Takeda, T., Yoshimura, K., Ishikawa, T. and Shigeoka, S. Feedback inhibition of spinach L-galactose dehydrogenase by L-ascorbate. Plant Cell Physiol. 45 (2004) 1271–1279. [DOI] [PMID: 15509850]
2.	Gatzek, S., Wheeler, G.L. and Smirnoff, N. Antisense suppression of L-galactose dehydrogenase in Arabidopsis thaliana provides evidence for its role in ascorbate synthesis and reveals light modulated L-galactose synthesis. Plant J. 30 (2002) 541–553. [DOI] [PMID: 12047629]
3.	Wheeler, G.L., Jones, M.A. and Smirnoff, N. The biosynthetic pathway of vitamin C in higher plants. Nature 393 (1998) 365–369. [DOI] [PMID: 9620799]
4.	Oh, M.M., Carey, E.E. and Rajashekar, C.B. Environmental stresses induce health-promoting phytochemicals in lettuce. Plant Physiol. Biochem. 47 (2009) 578–583. [DOI] [PMID: 19297184]

[EC 1.1.1.316 created 2011]

1.1.1.317

Accepted name:

perakine reductase

Reaction:

raucaffrinoline + NADP⁺ = perakine + NADPH + H⁺

For diagram of peraksine biosynthesis, click here

Glossary:

raucaffrinoline = (17R,20α,21β)-1,2-didehydro-1-demethyl-19-hydroxy-21-methyl-18-norajmalan-17-yl acetate
perakine = raucaffrine = (17R,20α,21β)-1,2-didehydro-1-demethyl-17-(acetyloxy)-21-methyl-18-norajmalan-19-al

Systematic name:

raucaffrinoline:NADP⁺ oxidoreductase

Comments:

The biosynthesis of raucaffrinoline from perakine is a side route of the ajmaline biosynthesis pathway. The enzyme is a member of the aldo-keto reductase enzyme superfamily from higher plants.

Links to other databases:

References:

1.	Sun, L., Ruppert, M., Sheludko, Y., Warzecha, H., Zhao, Y. and Stockigt, J. Purification, cloning, functional expression and characterization of perakine reductase: the first example from the AKR enzyme family, extending the alkaloidal network of the plant Rauvolfia. Plant Mol. Biol. 67 (2008) 455–467. [DOI] [PMID: 18409028]
2.	Rosenthal, C., Mueller, U., Panjikar, S., Sun, L., Ruppert, M., Zhao, Y. and Stockigt, J. Expression, purification, crystallization and preliminary X-ray analysis of perakine reductase, a new member of the aldo-keto reductase enzyme superfamily from higher plants. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 62 (2006) 1286–1289. [DOI] [PMID: 17142919]

[EC 1.1.1.317 created 2011]

1.1.3.42

Accepted name:

prosolanapyrone-II oxidase

Reaction:

prosolanapyrone II + O₂ = prosolanapyrone III + H₂O₂

For diagram of solanapyrone biosynthesis, click here

Glossary:

prosolanapyrone II = 3-(hydroxymethyl)-4-methoxy-6-(1E,7E,9E)-undeca-1,7,9-trien-1-yl-2H-pyran-2-one
prosolanapyrone III = 4-methoxy-2-oxo-6-(1E,7E,9E)-undeca-1,7,9-trien-1-yl-2H-pyran-3-carboxaldehyde

Other name(s):

Sol5 (ambiguous); SPS (ambiguous); solanapyrone synthase (bifunctional enzyme: prosolanapyrone II oxidase/prosolanapyrone III cycloisomerase); prosolanapyrone II oxidase

Systematic name:

prosolanapyrone-II:oxygen 3′-oxidoreductase

Comments:

The enzyme is involved in the biosynthesis of the phytotoxin solanapyrone by some fungi. The bifunctional enzyme catalyses the oxidation of prosolanapyrone II and the subsequent Diels Alder cycloisomerization of the product prosolanapyrone III to (-)-solanapyrone A (cf. EC 5.5.1.20, prosolanapyrone III cycloisomerase).

Links to other databases:

References:

1.	Kasahara, K., Miyamoto, T., Fujimoto, T., Oguri, H., Tokiwano, T., Oikawa, H., Ebizuka, Y. and Fujii, I. Solanapyrone synthase, a possible Diels-Alderase and iterative type I polyketide synthase encoded in a biosynthetic gene cluster from Alternaria solani. ChemBioChem 11 (2010) 1245–1252. [DOI] [PMID: 20486243]
2.	Katayama, K., Kobayashi, T., Oikawa, H., Honma, M. and Ichihara, A. Enzymatic activity and partial purification of solanapyrone synthase: first enzyme catalyzing Diels-Alder reaction. Biochim. Biophys. Acta 1384 (1998) 387–395. [DOI] [PMID: 9659400]
3.	Katayama, K., Kobayashi, T., Chijimatsu, M., Ichihara, A. and Oikawa, H. Purification and N-terminal amino acid sequence of solanapyrone synthase, a natural Diels-Alderase from Alternaria solani. Biosci. Biotechnol. Biochem. 72 (2008) 604–607. [DOI] [PMID: 18256508]

[EC 1.1.3.42 created 2011]

1.1 Acting on the CH-OH group of donors

1.1.9 With a copper protein as acceptor

1.1.9.1

Accepted name:

alcohol dehydrogenase (azurin)

Reaction:

a primary alcohol + azurin = an aldehyde + reduced azurin

Other name(s):

type II quinoprotein alcohol dehydrogenase; quinohaemoprotein ethanol dehydrogenase; QHEDH; ADHIIB

Systematic name:

alcohol:azurin oxidoreductase

Comments:

A soluble, periplasmic PQQ-containing quinohemoprotein. Also contains a single heme c. Occurs in Comamonas and Pseudomonas. Does not require an amine activator. Oxidizes a wide range of primary and secondary alcohols, and also aldehydes and large substrates such as sterols; methanol is not a substrate. Usually assayed with phenazine methosulfate or ferricyanide. Like all other quinoprotein alcohol dehydrogenases it has an 8-bladed ‘propeller’ structure, a calcium ion bound to the PQQ in the active site and an unusual disulfide ring structure in close proximity to the PQQ.

Links to other databases:

References:

1.	Groen, B.W., van Kleef, M.A. and Duine, J.A. Quinohaemoprotein alcohol dehydrogenase apoenzyme from Pseudomonas testosteroni. Biochem. J. 234 (1986) 611–615. [PMID: 3521592]
2.	de Jong, G.A., Caldeira, J., Sun, J., Jongejan, J.A., de Vries, S., Loehr, T.M., Moura, I., Moura, J.J. and Duine, J.A. Characterization of the interaction between PQQ and heme c in the quinohemoprotein ethanol dehydrogenase from Comamonas testosteroni. Biochemistry 34 (1995) 9451–9458. [PMID: 7626615]
3.	Toyama, H., Fujii, A., Matsushita, K., Shinagawa, E., Ameyama, M. and Adachi, O. Three distinct quinoprotein alcohol dehydrogenases are expressed when Pseudomonas putida is grown on different alcohols. J. Bacteriol. 177 (1995) 2442–2450. [DOI] [PMID: 7730276]
4.	Matsushita, K., Yamashita, T., Aoki, N., Toyama, H. and Adachi, O. Electron transfer from quinohemoprotein alcohol dehydrogenase to blue copper protein azurin in the alcohol oxidase respiratory chain of Pseudomonas putida HK5. Biochemistry 38 (1999) 6111–6118. [DOI] [PMID: 10320337]
5.	Chen, Z.W., Matsushita, K., Yamashita, T., Fujii, T.A., Toyama, H., Adachi, O., Bellamy, H.D. and Mathews, F.S. Structure at 1.9 Å resolution of a quinohemoprotein alcohol dehydrogenase from Pseudomonas putida HK5. Structure 10 (2002) 837–849. [DOI] [PMID: 12057198]
6.	Oubrie, A., Rozeboom, H.J., Kalk, K.H., Huizinga, E.G. and Dijkstra, B.W. Crystal structure of quinohemoprotein alcohol dehydrogenase from Comamonas testosteroni: structural basis for substrate oxidation and electron transfer. J. Biol. Chem. 277 (2002) 3727–3732. [DOI] [PMID: 11714714]

[EC 1.1.9.1 created 2010 as EC 1.1.98.1; transferred 2011 to EC 1.1.9.1]

1.1.98.1

Transferred entry:

Now EC 1.1.9.1, alcohol dehydrogenase (azurin)

[EC 1.1.98.1 created 2010, deleted 2011]

1.2.1.82

Accepted name:

β-apo-4′-carotenal dehydrogenase

Reaction:

4′-apo-β,ψ-caroten-4′-al + NAD⁺ + H₂O = neurosporaxanthin + NADH + 2 H⁺

For diagram of reaction, click here

Glossary:

neurosporaxanthin = 4′-apo-β,ψ-caroten-4′-oic acid

Other name(s):

β-apo-4′-carotenal oxygenase; YLO-1; carD (gene name)

Systematic name:

4′-apo-β,ψ-carotenal:NAD⁺ oxidoreductase

Comments:

Neurosporaxanthin is responsible for the orange color of of Neurospora.

Links to other databases:

References:

1.	Estrada, A.F., Youssar, L., Scherzinger, D., Al-Babili, S. and Avalos, J. The ylo-1 gene encodes an aldehyde dehydrogenase responsible for the last reaction in the Neurospora carotenoid pathway. Mol. Microbiol. 69 (2008) 1207–1220. [DOI] [PMID: 18627463]
2.	Diaz-Sanchez, V., Estrada, A.F., Trautmann, D., Al-Babili, S. and Avalos, J. The gene carD encodes the aldehyde dehydrogenase responsible for neurosporaxanthin biosynthesis in Fusarium fujikuroi. FEBS J. 278 (2011) 3164–3176. [DOI] [PMID: 21749649]

[EC 1.2.1.82 created 2011, modified 2023]

1.3.1.88

Accepted name:

tRNA-dihydrouridine^16/17 synthase [NAD(P)⁺]

Reaction:

(1) 5,6-dihydrouracil¹⁶ in tRNA + NAD(P)⁺ = uracil¹⁶ in tRNA + NAD(P)H + H⁺
(2) 5,6-dihydrouracil¹⁷ in tRNA + NAD(P)⁺ = uracil¹⁷ in tRNA + NAD(P)H + H⁺

Other name(s):

Dus1p; tRNA-dihydrouridine synthase 1

Systematic name:

tRNA-5,6-dihydrouracil^16/17:NAD(P)⁺ oxidoreductase

Comments:

A flavoprotein. The enzyme specifically modifies uracil¹⁶ and uracil¹⁷ in tRNA.

Links to other databases:

References:

1.	Xing, F., Hiley, S.L., Hughes, T.R. and Phizicky, E.M. The specificities of four yeast dihydrouridine synthases for cytoplasmic tRNAs. J. Biol. Chem. 279 (2004) 17850–17860. [DOI] [PMID: 14970222]
2.	Xing, F., Martzen, M.R. and Phizicky, E.M. A conserved family of Saccharomyces cerevisiae synthases effects dihydrouridine modification of tRNA. RNA 8 (2002) 370–381. [PMID: 12003496]

[EC 1.3.1.88 created 2011]

1.3.1.89

Accepted name:

tRNA-dihydrouridine⁴⁷ synthase [NAD(P)⁺]

Reaction:

5,6-dihydrouracil⁴⁷ in tRNA + NAD(P)⁺ = uracil⁴⁷ in tRNA + NAD(P)H + H⁺

Other name(s):

Dus3p; tRNA-dihydrouridine synthase 3

Systematic name:

tRNA-5,6-dihydrouracil⁴⁷:NAD(P)⁺ oxidoreductase

Comments:

A flavoenzyme. The enzyme specifically modifies uracil⁴⁷ in tRNA.

Links to other databases:

References:

1.	Xing, F., Hiley, S.L., Hughes, T.R. and Phizicky, E.M. The specificities of four yeast dihydrouridine synthases for cytoplasmic tRNAs. J. Biol. Chem. 279 (2004) 17850–17860. [DOI] [PMID: 14970222]

[EC 1.3.1.89 created 2011]

1.3.1.90

Accepted name:

tRNA-dihydrouridine^20a/20b synthase [NAD(P)⁺]

Reaction:

(1) 5,6-dihydrouracil^20a in tRNA + NAD(P)⁺ = uracil^20a in tRNA + NAD(P)H + H⁺
(2) 5,6-dihydrouracil^20b in tRNA + NAD(P)⁺ = uracil^20b in tRNA + NAD(P)H + H⁺

Other name(s):

Dus4p

Systematic name:

tRNA-5,6-dihydrouracil^20a/20b:NAD(P)⁺ oxidoreductase

Comments:

A flavoenzyme. The enzyme specifically modifies uracil^20a and uracil^20b in tRNA.

Links to other databases:

References:

1.	Xing, F., Hiley, S.L., Hughes, T.R. and Phizicky, E.M. The specificities of four yeast dihydrouridine synthases for cytoplasmic tRNAs. J. Biol. Chem. 279 (2004) 17850–17860. [DOI] [PMID: 14970222]

[EC 1.3.1.90 created 2011]

1.3.1.91

Accepted name:

tRNA-dihydrouridine²⁰ synthase [NAD(P)⁺]

Reaction:

5,6-dihydrouracil²⁰ in tRNA + NAD(P)⁺ = uracil²⁰ in tRNA + NAD(P)H + H⁺

Other name(s):

Dus2p; tRNA-dihydrouridine synthase 2

Systematic name:

tRNA-5,6-dihydrouracil²⁰:NAD(P)⁺ oxidoreductase

Comments:

A flavoenzyme [3]. The enzyme specifically modifies uracil²⁰ in tRNA.

Links to other databases:

References:

1.	Xing, F., Hiley, S.L., Hughes, T.R. and Phizicky, E.M. The specificities of four yeast dihydrouridine synthases for cytoplasmic tRNAs. J. Biol. Chem. 279 (2004) 17850–17860. [DOI] [PMID: 14970222]
2.	Xing, F., Martzen, M.R. and Phizicky, E.M. A conserved family of Saccharomyces cerevisiae synthases effects dihydrouridine modification of tRNA. RNA 8 (2002) 370–381. [PMID: 12003496]
3.	Rider, L.W., Ottosen, M.B., Gattis, S.G. and Palfey, B.A. Mechanism of dihydrouridine synthase 2 from yeast and the importance of modifications for efficient tRNA reduction. J. Biol. Chem. 284 (2009) 10324–10333. [DOI] [PMID: 19139092]
4.	Kato, T., Daigo, Y., Hayama, S., Ishikawa, N., Yamabuki, T., Ito, T., Miyamoto, M., Kondo, S. and Nakamura, Y. A novel human tRNA-dihydrouridine synthase involved in pulmonary carcinogenesis. Cancer Res. 65 (2005) 5638–5646. [DOI] [PMID: 15994936]

[EC 1.3.1.91 created 2011]

*EC

1.3.8.2

Accepted name:

4,4′-diapophytoene desaturase (4,4′-diapolycopene-forming)

Reaction:

15-cis-4,4′-diapophytoene + 4 FAD = all-trans-4,4′-diapolycopene + 4 FADH₂ (overall reaction)
(1a) 15-cis-4,4′-diapophytoene + FAD = all-trans-4,4′-diapophytofluene + FADH₂
(1b) all-trans-4,4′-diapophytofluene + FAD = all-trans-4,4′-diapo-ζ-carotene + FADH₂
(1c) all-trans-4,4′-diapo-ζ-carotene + FAD = all-trans-4,4′-diaponeurosporene + FADH₂
(1d) all-trans-4,4′-diaponeurosporene + FAD = all-trans-4,4′-diapolycopene + FADH₂

For diagram of C₃₀ carotenoid biosynthesis, click here

Other name(s):

dehydrosqualene desaturase (ambiguous); CrtN (ambiguous); 4,4′-diapophytoene:FAD oxidoreductase (ambiguous); 15-cis-4,4′-diapophytoene:FAD oxidoreductase; 4,4′-diapophytoene desaturase (ambiguous)

Systematic name:

15-cis-4,4′-diapophytoene:FAD oxidoreductase (4,4′-diapolycopene-forming)

Comments:

The enzyme catalyses four successive dehydrogenations, resulting in production of 4,4′-diapolycopene. While the enzyme from Staphylococcus aureus was only shown to produce 4,4′-diaponeurosporene in vivo [4], it is able to catalyse the last reaction in vitro [5].

Links to other databases:

References:

1.	Wieland, B., Feil, C., Gloria-Maercker, E., Thumm, G., Lechner, M., Bravo, J.M., Poralla, K. and Gotz, F. Genetic and biochemical analyses of the biosynthesis of the yellow carotenoid 4,4′-diaponeurosporene of Staphylococcus aureus. J. Bacteriol. 176 (1994) 7719–7726. [DOI] [PMID: 8002598]
2.	Raisig, A. and Sandmann, G. 4,4′-diapophytoene desaturase: catalytic properties of an enzyme from the C₃₀ carotenoid pathway of Staphylococcus aureus. J. Bacteriol. 181 (1999) 6184–6187. [PMID: 10498735]
3.	Raisig, A. and Sandmann, G. Functional properties of diapophytoene and related desaturases of C₃₀ to C₄₀ carotenoid biosynthetic pathways. Biochim. Biophys. Acta 1533 (2001) 164–170. [DOI] [PMID: 11566453]
4.	Tao, L., Schenzle, A., Odom, J.M. and Cheng, Q. Novel carotenoid oxidase involved in biosynthesis of 4,4′-diapolycopene dialdehyde. Appl. Environ. Microbiol. 71 (2005) 3294–3301. [DOI] [PMID: 15933032]
5.	Yoshida, K., Ueda, S. and Maeda, I. Carotenoid production in Bacillus subtilis achieved by metabolic engineering. Biotechnol. Lett. 31 (2009) 1789–1793. [DOI] [PMID: 19618272]

[EC 1.3.8.2 created 2011, modified 2011]

1.4 Acting on the CH-NH₂ group of donors

1.4.9 With a copper protein as acceptor

1.4.9.1

Accepted name:

methylamine dehydrogenase (amicyanin)

Reaction:

methylamine + H₂O + 2 amicyanin = formaldehyde + NH₃ + 2 reduced amicyanin

Glossary:

TTQ = tryptophan tryptophylquinone
amicyanin = an electron-transfer protein containing a type-1 copper site.

Other name(s):

amine dehydrogenase; primary-amine dehydrogenase; amine: (acceptor) oxidoreductase (deaminating); primary-amine:(acceptor) oxidoreductase (deaminating)

Systematic name:

methylamine:amicyanin oxidoreductase (deaminating)

Comments:

Contains tryptophan tryptophylquinone (TTQ) cofactor. The enzyme oxidizes aliphatic monoamines and diamines, histamine and ethanolamine, but not secondary and tertiary amines, quaternary ammonium salts or aromatic amines.

Links to other databases:

References:

1.	De Beer, R., Duine, J.A., Frank, J., Jr. and Large, P.J. The prosthetic group of methylamine dehydrogenase from Pseudomonas AM1: evidence for a quinone structure. Biochim. Biophys. Acta 622 (1980) 370–374. [DOI] [PMID: 6246962]
2.	Eady, R.R. and Large, P.J. Purification and properties of an amine dehydrogenase from Pseudomonas AM1 and its role in growth on methylamine. Biochem. J. 106 (1968) 245–255. [PMID: 4388687]
3.	Eady, R.R. and Large, P.J. Microbial oxidation of amines. Spectral and kinetic properties of the primary amine dehydrogenase of Pseudomonas AM1. Biochem. J. 123 (1971) 757–771. [PMID: 5124384]
4.	Cavalieri, C., Biermann, N., Vlasie, M.D., Einsle, O., Merli, A., Ferrari, D., Rossi, G.L. and Ubbink, M. Structural comparison of crystal and solution states of the 138 kDa complex of methylamine dehydrogenase and amicyanin from Paracoccus versutus. Biochemistry 47 (2008) 6560–6570. [DOI] [PMID: 18512962]
5.	Meschi, F., Wiertz, F., Klauss, L., Cavalieri, C., Blok, A., Ludwig, B., Heering, H.A., Merli, A., Rossi, G.L. and Ubbink, M. Amicyanin transfers electrons from methylamine dehydrogenase to cytochrome c-551i via a ping-pong mechanism, not a ternary complex. J. Am. Chem. Soc. 132 (2010) 14537–14545. [DOI] [PMID: 20873742]

[EC 1.4.9.1 created 1978 as EC 1.4.99.3, modified 1986, transferred 2011 to EC 1.4.98.1, transferred 2011 to EC 1.4.9.1]

1.4.9.2

Accepted name:

aralkylamine dehydrogenase (azurin)

Reaction:

ArCH2NH2 + H₂O + 2 azurin = ArCHO + NH₃ + 2 reduced azurin

Glossary:

azurin = an electron-transfer protein containing a type-1 copper site

Other name(s):

aromatic amine dehydrogenase; arylamine dehydrogenase; tyramine dehydrogenase; aralkylamine:(acceptor) oxidoreductase (deaminating)

Systematic name:

aralkylamine:azurin oxidoreductase (deaminating)

Comments:

Phenazine methosulfate can act as acceptor. Acts on aromatic amines and, more slowly, on some long-chain aliphatic amines, but not on methylamine or ethylamine

Links to other databases:

References:

1.	Iwaki, M., Yagi, T., Horiike, K., Saeki, Y., Ushijima, T. and Nozaki, M. Crystallization and properties of aromatic amine dehydrogenase from Pseudomonas sp. Arch. Biochem. Biophys. 220 (1983) 253–262. [DOI] [PMID: 6830237]
2.	Hyun, Y.L. and Davidson, V.L. Electron transfer reactions between aromatic amine dehydrogenase and azurin. Biochemistry 34 (1995) 12249–12254. [PMID: 7547967]
3.	Hyun, Y.L., Zhu, Z. and Davidson, V.L. Gated and ungated electron transfer reactions from aromatic amine dehydrogenase to azurin. J. Biol. Chem. 274 (1999) 29081–29086. [DOI] [PMID: 10506161]
4.	Davidson, V.L. Electron transfer in quinoproteins. Arch. Biochem. Biophys. 428 (2004) 32–40. [DOI] [PMID: 15234267]
5.	Sukumar, N., Chen, Z.W., Ferrari, D., Merli, A., Rossi, G.L., Bellamy, H.D., Chistoserdov, A., Davidson, V.L. and Mathews, F.S. Crystal structure of an electron transfer complex between aromatic amine dehydrogenase and azurin from Alcaligenes faecalis. Biochemistry 45 (2006) 13500–13510. [DOI] [PMID: 17087503]

[EC 1.4.9.2 created 1986 as EC 1.4.99.4, transferred 2011 to EC 1.4.9.2]

1.4.98.1

Transferred entry:

amine dehydrogenase. Now EC 1.4.9.1, methylamine dehydrogenase (amicyanin)

[EC 1.4.98.1 created 1978 as EC 1.4.99.3, modified 1986, transferred 2011 to EC 1.4.98.1, deleted 2011]

1.4.99.4

Transferred entry:

aralkylamine dehydrogenase. Now EC 1.4.9.2, aralkylamine dehydrogenase (azurin)

[EC 1.4.99.4 created 1986, deleted 2011]

1.5.1.29

Deleted entry:

FMN reductase [NAD(P)H]. Now covered by EC 1.5.1.38 [FMN reductase (NADPH)], EC 1.5.1.39 [FMN reductase [NAD(P)H])] and EC 1.5.1.41 (riboflavin reductase [NAD(P)H])

[EC 1.5.1.29 created 1981 as EC 1.6.8.1, transferred 2002 to EC 1.5.1.29, modified 2002, deleted 2011]

1.5.1.37

Accepted name:

FAD reductase (NADH)

Reaction:

FADH₂ + NAD⁺ = FAD + NADH + H⁺

For diagram of FAD biosynthesis, click here

Other name(s):

NADH-FAD reductase; NADH-dependent FAD reductase; NADH:FAD oxidoreductase; NADH:flavin adenine dinucleotide oxidoreductase

Systematic name:

FADH₂:NAD⁺ oxidoreductase

Comments:

The enzyme from Burkholderia phenoliruptrix can reduce either FAD or flavin mononucleotide (FMN) but prefers FAD. Unlike EC 1.5.1.36, flavin reductase (NADH), the enzyme can not reduce riboflavin. The enzyme does not use NADPH as acceptor.

Links to other databases:

References:

1.	Gisi, M.R. and Xun, L. Characterization of chlorophenol 4-monooxygenase (TftD) and NADH:flavin adenine dinucleotide oxidoreductase (TftC) of Burkholderia cepacia AC1100. J. Bacteriol. 185 (2003) 2786–2792. [DOI] [PMID: 12700257]

[EC 1.5.1.37 created 2011]

1.5.1.38

Accepted name:

FMN reductase (NADPH)

Reaction:

FMNH₂ + NADP⁺ = FMN + NADPH + H⁺

For diagram of FAD biosynthesis, click here

Other name(s):

FRP; flavin reductase P; SsuE

Systematic name:

FMNH₂:NADP⁺ oxidoreductase

Comments:

The enzymes from bioluminescent bacteria contain FMN [4], while the enzyme from Escherichia coli does not [8]. The enzyme often forms a two-component system with monooxygenases such as luciferase. Unlike EC 1.5.1.39, this enzyme does not use NADH as acceptor [1,2]. While FMN is the preferred substrate, the enzyme can also use FAD and riboflavin with lower activity [3,6,8].

Links to other databases:

References:

1.	Gerlo, E. and Charlier, J. Identification of NADH-specific and NADPH-specific FMN reductases in Beneckea harveyi. Eur. J. Biochem. 57 (1975) 461–467. [DOI] [PMID: 1175652]
2.	Jablonski, E. and DeLuca, M. Purification and properties of the NADH and NADPH specific FMN oxidoreductases from Beneckea harveyi. Biochemistry 16 (1977) 2932–2936. [PMID: 880288]
3.	Jablonski, E. and DeLuca, M. Studies of the control of luminescence in Beneckea harveyi: properties of the NADH and NADPH:FMN oxidoreductases. Biochemistry 17 (1978) 672–678. [PMID: 23827]
4.	Lei, B., Liu, M., Huang, S. and Tu, S.C. Vibrio harveyi NADPH-flavin oxidoreductase: cloning, sequencing and overexpression of the gene and purification and characterization of the cloned enzyme. J. Bacteriol. 176 (1994) 3552–3558. [DOI] [PMID: 8206832]
5.	Tanner, J.J., Lei, B., Tu, S.C. and Krause, K.L. Flavin reductase P: structure of a dimeric enzyme that reduces flavin. Biochemistry 35 (1996) 13531–13539. [DOI] [PMID: 8885832]
6.	Liu, M., Lei, B., Ding, Q., Lee, J.C. and Tu, S.C. Vibrio harveyi NADPH:FMN oxidoreductase: preparation and characterization of the apoenzyme and monomer-dimer equilibrium. Arch. Biochem. Biophys. 337 (1997) 89–95. [DOI] [PMID: 8990272]
7.	Lei, B. and Tu, S.C. Mechanism of reduced flavin transfer from Vibrio harveyi NADPH-FMN oxidoreductase to luciferase. Biochemistry 37 (1998) 14623–14629. [DOI] [PMID: 9772191]
8.	Eichhorn, E., van der Ploeg, J.R. and Leisinger, T. Characterization of a two-component alkanesulfonate monooxygenase from Escherichia coli. J. Biol. Chem. 274 (1999) 26639–26646. [DOI] [PMID: 10480865]

[EC 1.5.1.38 created 2011]

1.5.1.39

Accepted name:

FMN reductase [NAD(P)H]

Reaction:

FMNH₂ + NAD(P)⁺ = FMN + NAD(P)H + H⁺

For diagram of FAD biosynthesis, click here

Other name(s):

FRG

Systematic name:

FMNH₂:NAD(P)⁺ oxidoreductase

Comments:

Contains FMN. The enzyme can utilize NADH and NADPH with similar reaction rates. Different from EC 1.5.1.42, FMN reductase (NADH) and EC 1.5.1.38, FMN reductase (NADPH). The luminescent bacterium Vibrio harveyi possesses all three enzymes [1]. Also reduces riboflavin and FAD, but more slowly.

Links to other databases:

References:

1.	Watanabe, H. and Hastings, J.W. Specificities and properties of three reduced pyridine nucleotide-flavin mononucleotide reductases coupling to bacterial luciferase. Mol. Cell. Biochem. 44 (1982) 181–187. [PMID: 6981058]

[EC 1.5.1.39 created 2011]

1.5.1.40

Accepted name:

8-hydroxy-5-deazaflavin:NADPH oxidoreductase

Reaction:

reduced coenzyme F₄₂₀ + NADP⁺ = oxidized coenzyme F₄₂₀ + NADPH + H⁺

For diagram of coenzyme F₄₂₀ biosynthesis, click here

Other name(s):

8-OH-5dFl:NADPH oxidoreductase

Systematic name:

reduced coenzyme F₄₂₀:NADP⁺ oxidoreductase

Comments:

The enzyme has an absolute requirement for both the 5-deazaflavin structure and the presence of an 8-hydroxy group in the substrate [1].

Links to other databases:

References:

1.	Eker, A.P., Hessels, J.K. and Meerwaldt, R. Characterization of an 8-hydroxy-5-deazaflavin:NADPH oxidoreductase from Streptomyces griseus. Biochim. Biophys. Acta 990 (1989) 80–86. [DOI] [PMID: 2492438]

[EC 1.5.1.40 created 2011]

1.5.1.41

Accepted name:

riboflavin reductase [NAD(P)H]

Reaction:

reduced riboflavin + NAD(P)⁺ = riboflavin + NAD(P)H + H⁺

For diagram of riboflavin biosynthesis (late stages), click here

Other name(s):

NAD(P)H-FMN reductase (ambiguous); NAD(P)H-dependent FMN reductase (ambiguous); NAD(P)H:FMN oxidoreductase (ambiguous); NAD(P)H:flavin oxidoreductase (ambiguous); NAD(P)H₂ dehydrogenase (FMN) (ambiguous); NAD(P)H₂:FMN oxidoreductase (ambiguous); riboflavin mononucleotide reductase (ambiguous); flavine mononucleotide reductase (ambiguous); riboflavin mononucleotide (reduced nicotinamide adenine dinucleotide (phosphate)) reductase; flavin mononucleotide reductase (ambiguous); riboflavine mononucleotide reductase (ambiguous); Fre

Systematic name:

riboflavin:NAD(P)⁺ oxidoreductase

Comments:

Catalyses the reduction of soluble flavins by reduced pyridine nucleotides. Highest activity with riboflavin. When NADH is used as acceptor, the enzyme can also utilize FMN and FAD as substrates, with lower activity than riboflavin. When NADPH is used as acceptor, the enzyme has a very low activity with FMN and no activity with FAD [1].

Links to other databases:

References:

1.	Fontecave, M., Eliasson, R. and Reichard, P. NAD(P)H:flavin oxidoreductase of Escherichia coli. A ferric iron reductase participating in the generation of the free radical of ribonucleotide reductase. J. Biol. Chem. 262 (1987) 12325–12331. [PMID: 3305505]
2.	Spyrou, G., Haggård-Ljungquist, E., Krook, M., Jörnvall, H., Nilsson, E. and Reichard, P. Characterization of the flavin reductase gene (fre) of Escherichia coli and construction of a plasmid for overproduction of the enzyme. J. Bacteriol. 173 (1991) 3673–3679. [DOI] [PMID: 2050627]
3.	Ingelman, M., Ramaswamy, S., Nivière, V., Fontecave, M. and Eklund, H. Crystal structure of NAD(P)H:flavin oxidoreductase from Escherichia coli. Biochemistry 38 (1999) 7040–7049. [DOI] [PMID: 10353815]

[EC 1.5.1.41 created 2011]

1.5.1.42

Accepted name:

FMN reductase (NADH)

Reaction:

FMNH₂ + NAD⁺ = FMN + NADH + H⁺

For diagram of FAD biosynthesis, click here

Other name(s):

NADH-FMN reductase; NADH-dependent FMN reductase; NADH:FMN oxidoreductase; NADH:flavin oxidoreductase

Systematic name:

FMNH₂:NAD⁺ oxidoreductase

Comments:

The enzyme often forms a two-component system with monooxygenases. Unlike EC 1.5.1.38, FMN reductase (NADPH), and EC 1.5.1.39, FMN reductase [NAD(P)H], this enzyme has a strong preference for NADH over NADPH, although some activity with the latter is observed [1,2]. While FMN is the preferred substrate, FAD can also be used with much lower activity [1,3].

Links to other databases:

References:

1.	Duane, W. and Hastings, J.W. Flavin mononucleotide reductase of luminous bacteria. Mol. Cell. Biochem. 6 (1975) 53–64. [PMID: 47604]
2.	Gerlo, E. and Charlier, J. Identification of NADH-specific and NADPH-specific FMN reductases in Beneckea harveyi. Eur. J. Biochem. 57 (1975) 461–467. [DOI] [PMID: 1175652]
3.	Uetz, T., Schneider, R., Snozzi, M. and Egli, T. Purification and characterization of a two-component monooxygenase that hydroxylates nitrilotriacetate from "Chelatobacter" strain ATCC 29600. J. Bacteriol. 174 (1992) 1179–1188. [DOI] [PMID: 1735711]
4.	Izumoto, Y., Mori, T. and Yamamoto, K. Cloning and nucleotide sequence of the gene for NADH:FMN oxidoreductase from Vibrio harveyi. Biochim. Biophys. Acta 1185 (1994) 243–246. [DOI] [PMID: 8167139]

[EC 1.5.1.42 created 2011]

1.6.5.10

Accepted name:

NADPH dehydrogenase (quinone)

Reaction:

NADPH + H⁺ + a quinone = NADP⁺ + a quinol

Other name(s):

reduced nicotinamide adenine dinucleotide phosphate (quinone) dehydrogenase; NADPH oxidase; NADPH₂ dehydrogenase (quinone)

Systematic name:

NADPH:(quinone-acceptor) oxidoreductase

Comments:

A flavoprotein [1, 2]. The enzyme from Escherichia coli is specific for NADPH and is most active with quinone derivatives and ferricyanide as electron acceptors [3]. Menaquinone can act as acceptor. The enzyme from hog liver is inhibited by dicoumarol and folic acid derivatives but not by 2,4-dinitrophenol [1].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 37256-37-4

References:

1.	Koli, A.K., Yearby, C., Scott, W. and Donaldson, K.O. Purification and properties of three separate menadione reductases from hog liver. J. Biol. Chem. 244 (1969) 621–629. [PMID: 4388793]
2.	Hayashi, M., Hasegawa, K., Oguni, Y. and Unemoto, T. Characterization of FMN-dependent NADH-quinone reductase induced by menadione in Escherichia coli. Biochim. Biophys. Acta 1035 (1990) 230–236. [DOI] [PMID: 2118386]
3.	Hayashi, M., Ohzeki, H., Shimada, H. and Unemoto, T. NADPH-specific quinone reductase is induced by 2-methylene-4-butyrolactone in Escherichia coli. Biochim. Biophys. Acta 1273 (1996) 165–170. [DOI] [PMID: 8611590]

[EC 1.6.5.10 created 1972 as EC 1.6.99.6, transferred 2011 to EC 1.6.5.10]

1.6.99.6

Transferred entry:

NADPH dehydrogenase (quinone). Now EC 1.6.5.10, NADPH dehydrogenase (quinone)

[EC 1.6.99.6 created 1972, deleted 2011]

1.7 Acting on other nitrogenous compounds as donors

1.7.6 With a nitrogenous group as acceptor

1.7.6.1

Accepted name:

nitrite dismutase

Reaction:

3 nitrite + 2 H⁺ = 2 nitric oxide + nitrate + H₂O

Other name(s):

Prolixin S; Nitrophorin 7

Systematic name:

nitrite:nitrite oxidoreductase

Comments:

Contains ferriheme b. The enzyme is one of the nitrophorins from the salivary gland of the blood-feeding insect Rhodnius prolixus. Nitric oxide produced induces vasodilation after injection. Nitrophorins 2 and 4 can also catalyse this reaction.

Links to other databases:

References:

1.	He, C. and Knipp, M. Formation of nitric oxide from nitrite by the ferriheme b protein nitrophorin 7. J. Am. Chem. Soc. 131 (2009) 12042–12043. [DOI] [PMID: 19655755]
2.	He, C., Ogata, H. and Knipp, M. Formation of the complex of nitrite with the ferriheme b β-barrel proteins nitrophorin 4 and nitrophorin 7. Biochemistry 49 (2010) 5841–5851. [DOI] [PMID: 20524697]

[EC 1.7.6.1 created 2011]

1.10 Acting on diphenols and related substances as donors

1.10.9 With a copper protein as acceptor

1.10.9.1

Transferred entry:

plastoquinol—plastocyanin reductase. Now EC 7.1.1.6, plastoquinol—plastocyanin reductase

[EC 1.10.9.1 created 1984 as EC 1.10.99.1, transferred 2011 to EC 1.10.9.1, deleted 2018]

1.10.99.1

Transferred entry:

Now EC 1.10.9.1 plastoquinol—plastocyanin reductase

[EC 1.10.99.1 created 1984, deleted 2011]

*EC

1.13.11.16

Accepted name:

3-carboxyethylcatechol 2,3-dioxygenase

Reaction:

(1) 3-(2,3-dihydroxyphenyl)propanoate + O₂ = (2Z,4E)-2-hydroxy-6-oxonona-2,4-diene-1,9-dioate
(2) (2E)-3-(2,3-dihydroxyphenyl)prop-2-enoate + O₂ = (2Z,4E,7E)-2-hydroxy-6-oxonona-2,4,7-triene-1,9-dioate

For diagram of 3-phenylpropanoate catabolism, click here and for diagram of cinnamate catabolism, click here

Glossary:

(2E)-3-(2,3-dihydroxyphenyl)prop-2-enoate = trans-2,3-dihydroxycinnamate

Other name(s):

2,3-dihydroxy-β-phenylpropionic dioxygenase; 2,3-dihydroxy-β-phenylpropionate oxygenase; 3-(2,3-dihydroxyphenyl)propanoate:oxygen 1,2-oxidoreductase; 3-(2,3-dihydroxyphenyl)propanoate:oxygen 1,2-oxidoreductase (decyclizing)

Systematic name:

3-(2,3-dihydroxyphenyl)propanoate:oxygen 1,2-oxidoreductase (ring-opening)

Comments:

An iron protein. This enzyme catalyses a step in the pathway of phenylpropanoid compounds degradation.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 105503-63-7

References:

1.	Dagley, S., Chapman, P.J. and Gibson, D.T. The metabolism of β-phenylpropionic acid by an Achromobacter. Biochem. J. 97 (1965) 643–650. [PMID: 5881653]
2.	Lam, W. W. Y and Bugg, T. D. H. Chemistry of extradiol aromatic ring cleavage: isolation of a stable dienol ring fission intermediate and stereochemistry of its enzymatic hydrolytic clevage. J. Chem. Soc., Chem. Commun. 10 (1994) 1163–1164.
3.	Díaz, E., Ferrández, A. and García, J.L. Characterization of the hca cluster encoding the dioxygenolytic pathway for initial catabolism of 3-phenylpropionic acid in Escherichia coli K-12. J. Bacteriol. 180 (1998) 2915–2923. [PMID: 9603882]

[EC 1.13.11.16 created 1972, modified 2011, modified 2012]

*EC

1.13.11.26

Accepted name:

peptide-tryptophan 2,3-dioxygenase

Reaction:

[protein]-L-tryptophan + O₂ = [protein]-N-formyl-L-kynurenine

Glossary:

N-formyl-L-kynurenine = (2S)-2-amino-4-[2-(formamido)phenyl]-4-oxobutanoic acid

Other name(s):

pyrrolooxygenase; peptidyltryptophan 2,3-dioxygenase; tryptophan pyrrolooxygenase; [protein]-L-tryptophan:oxygen 2,3-oxidoreductase (decyclizing)

Systematic name:

[protein]-L-tryptophan:oxygen 2,3-oxidoreductase (ring-opening)

Comments:

Also acts on tryptophan.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 37256-64-7

References:

1.	Frydman, R.B., Tomaro, M.L. and Frydman, B. Pyrrolooxygenase: its action on tryptophan-containing enzymes and peptides. Biochim. Biophys. Acta 284 (1972) 80–89. [DOI] [PMID: 4403729]
2.	Camoretti-Mercado, B. and Frydman, R.B. Separation of tryptophan pyrrolooxygenase into three molecular forms. A study of their substrate specificities using tryptophyl-containing peptides and proteins. Eur. J. Biochem. 156 (1986) 317–325. [DOI] [PMID: 3699018]

[EC 1.13.11.26 created 1972, modified 2011]

1.13.11.44

Deleted entry:

linoleate diol synthase. Activity is covered by EC 1.13.11.60, linoleate 8R-lipoxygenase and EC 5.4.4.6, 9,12-octadecadienoate 8-hydroperoxide 8S-isomerase.

[EC 1.13.11.44 created 2000, deleted 2011]

1.13.11.59

Accepted name:

torulene dioxygenase

Reaction:

torulene + O₂ = 4′-apo-β,ψ-caroten-4′-al + 3-methylbut-2-enal

For diagram of reaction, click here

Glossary:

torulene = 3′,4′-didehydro-β,ψ-carotene

Other name(s):

CAO-2; CarT

Systematic name:

torulene:oxygen oxidoreductase

Comments:

It is assumed that 3-methylbut-2-enal is formed. The enzyme cannot cleave the saturated 3′,4′-bond of γ-carotene which implies that a 3′,4′-double bond is neccessary for this reaction.

Links to other databases:

References:

1.	Prado-Cabrero, A., Estrada, A.F., Al-Babili, S. and Avalos, J. Identification and biochemical characterization of a novel carotenoid oxygenase: elucidation of the cleavage step in the Fusarium carotenoid pathway. Mol. Microbiol. 64 (2007) 448–460. [DOI] [PMID: 17493127]
2.	Saelices, L., Youssar, L., Holdermann, I., Al-Babili, S. and Avalos, J. Identification of the gene responsible for torulene cleavage in the Neurospora carotenoid pathway. Mol. Genet. Genomics 278 (2007) 527–537. [DOI] [PMID: 17610084]
3.	Estrada, A.F., Maier, D., Scherzinger, D., Avalos, J. and Al-Babili, S. Novel apocarotenoid intermediates in Neurospora crassa mutants imply a new biosynthetic reaction sequence leading to neurosporaxanthin formation. Fungal Genet. Biol. 45 (2008) 1497–1505. [DOI] [PMID: 18812228]

[EC 1.13.11.59 created 2011]

1.13.11.60

Accepted name:

linoleate 8R-lipoxygenase

Reaction:

linoleate + O₂ = (8R,9Z,12Z)-8-hydroperoxyoctadeca-9,12-dienoate

Glossary:

linoleate = (9Z,12Z)-octadeca-9,12-dienoate

Other name(s):

linoleic acid 8R-dioxygenase; 5,8-LDS (bifunctional enzyme); 7,8-LDS (bifunctional enzyme); 5,8-linoleate diol synthase (bifunctional enzyme); 7,8-linoleate diol synthase (bifunctional enzyme); PpoA

Systematic name:

linoleate:oxygen (8R)-oxidoreductase

Comments:

The enzyme contains heme [1,4]. The bifunctional enzyme from Aspergillus nidulans uses different heme domains to catalyse two separate reactions. Linoleic acid is oxidized within the N-terminal heme peroxidase domain to (8R,9Z,12Z)-8-hydroperoxyoctadeca-9,12-dienoate, which is subsequently isomerized by the C-terminal P-450 heme thiolate domain to (5S,8R,9Z,12Z)-5,8-dihydroxyoctadeca-9,12-dienoate (cf. EC 5.4.4.5, 9,12-octadecadienoate 8-hydroperoxide 8R-isomerase) [1]. The bifunctional enzyme from Gaeumannomyces graminis also catalyses the oxidation of linoleic acid to (8R,9Z,12Z)-8-hydroperoxyoctadeca-9,12-dienoate, but its second domain isomerizes it to (7S,8S,9Z,12Z)-5,8-dihydroxyoctadeca-9,12-dienoate (cf. EC 5.4.4.6, 9,12-octadecadienoate 8-hydroperoxide 8S-isomerase) [4].

Links to other databases:

References:

1.	Brodhun, F., Gobel, C., Hornung, E. and Feussner, I. Identification of PpoA from Aspergillus nidulans as a fusion protein of a fatty acid heme dioxygenase/peroxidase and a cytochrome P₄₅₀. J. Biol. Chem. 284 (2009) 11792–11805. [DOI] [PMID: 19286665]
2.	Hamberg, M., Zhang, L.-Y., Brodowsky, I.D. and Oliw, E.H. Sequential oxygenation of linoleic acid in the fungus Gaeumannomyces graminis: stereochemistry of dioxygenase and hydroperoxide isomerase reactions. Arch. Biochem. Biophys. 309 (1994) 77–80. [DOI] [PMID: 8117115]
3.	Garscha, U. and Oliw, E. Pichia expression and mutagenesis of 7,8-linoleate diol synthase change the dioxygenase and hydroperoxide isomerase. Biochem. Biophys. Res. Commun. 373 (2008) 579–583. [DOI] [PMID: 18586008]
4.	Su, C. and Oliw, E.H. Purification and characterization of linoleate 8-dioxygenase from the fungus Gaeumannomyces graminis as a novel hemoprotein. J. Biol. Chem. 271 (1996) 14112–14118. [DOI] [PMID: 8662736]

[EC 1.13.11.60 created 2011]

1.13.11.61

Accepted name:

linolenate 9R-lipoxygenase

Reaction:

α-linolenate + O₂ = (9R,10E,12Z,15Z)-9-hydroperoxyoctadeca-10,12,15-trienoate

Glossary:

linoleate = (9Z,12Z)-octadeca-9,12-dienoate
α-linolenate = (9Z,12Z,15Z)-octadeca-9,12,15-trienoate

Other name(s):

NspLOX; (9R)-LOX; linoleate 9R-dioxygenase

Systematic name:

α-linolenate:oxygen (9R)-oxidoreductase

Comments:

In cyanobacteria the enzyme is involved in oxylipin biosynthesis. The enzyme also converts linoleate to (9R,10E,12Z)-9-hydroperoxyoctadeca-10,12-dienoate.

Links to other databases:

References:

1.	Jerneren, F., Hoffmann, I. and Oliw, E.H. Linoleate 9R-dioxygenase and allene oxide synthase activities of Aspergillus terreus. Arch. Biochem. Biophys. 495 (2010) 67–73. [DOI] [PMID: 20043865]
2.	Andreou, A.Z., Vanko, M., Bezakova, L. and Feussner, I. Properties of a mini 9R-lipoxygenase from Nostoc sp. PCC 7120 and its mutant forms. Phytochemistry 69 (2008) 1832–1837. [DOI] [PMID: 18439634]
3.	Lang, I., Gobel, C., Porzel, A., Heilmann, I. and Feussner, I. A lipoxygenase with linoleate diol synthase activity from Nostoc sp. PCC 7120. Biochem. J. 410 (2008) 347–357. [DOI] [PMID: 18031288]

[EC 1.13.11.61 created 2011]

1.13.11.62

Accepted name:

linoleate 10R-lipoxygenase

Reaction:

linoleate + O₂ = (8E,10R,12Z)-10-hydroperoxy-8,12-octadecadienoate

Glossary:

linoleate = (9Z,12Z)-octadeca-9,12-dienoate

Other name(s):

10R-DOX; (10R)-dioxygenase; 10R-dioxygenase

Systematic name:

linoleate:oxygen (10R)-oxidoreductase

Comments:

The enzyme is involved in biosynthesis of oxylipins, which affect sporulation, development, and pathogenicity of Aspergillus spp.

Links to other databases:

References:

1.	Garscha, U. and Oliw, E.H. Leucine/valine residues direct oxygenation of linoleic acid by (10R)- and (8R)-dioxygenases: expression and site-directed mutagenesis of (10R)-dioxygenase with epoxyalcohol synthase activity. J. Biol. Chem. 284 (2009) 13755–13765. [DOI] [PMID: 19289462]
2.	Jerneren, F., Garscha, U., Hoffmann, I., Hamberg, M. and Oliw, E.H. Reaction mechanism of 5,8-linoleate diol synthase, 10R-dioxygenase, and 8,11-hydroperoxide isomerase of Aspergillus clavatus. Biochim. Biophys. Acta 1801 (2010) 503–507. [DOI] [PMID: 20045744]

[EC 1.13.11.62 created 2011]

1.13.12.19

Accepted name:

2-oxoglutarate dioxygenase (ethene-forming)

Reaction:

2-oxoglutarate + O₂ = ethene + 3 CO₂ + H₂O

Glossary:

ethene = ethylene

Other name(s):

ethylene-forming enzyme; EFE; 2-oxoglutarate dioxygenase (ethylene-forming); 2-oxoglutarate:oxygen oxidoreductase (decarboxylating, ethylene-forming)

Systematic name:

2-oxoglutarate:oxygen oxidoreductase (decarboxylating, ethene-forming)

Comments:

This is one of two simultaneous reactions catalysed by the enzyme, which is responsible for ethene production in bacteria of the Pseudomonas syringae group. In the other reaction [EC 1.14.20.7, 2-oxoglutarate/L-arginine monooxygenase/decarboxylase (succinate-forming)] the enzyme catalyses the mono-oxygenation of both 2-oxoglutarate and L-arginine, forming succinate, carbon dioxide and 5-hydroxy-L-arginine, which is subsequently cleaved into guanidine and (S)-1-pyrroline-5-carboxylate.The enzymes catalyse two cycles of the ethene-forming reaction for each cycle of the succinate-forming reaction, so that the stoichiometry of the products ethene and succinate is 2:1.

Links to other databases:

References:

1.	Nagahama, K., Ogawa, T., Fujii, T., Tazaki, M., Tanase, S., Morino, Y. and Fukuda, H. Purification and properties of an ethylene-forming enzyme from Pseudomonas syringae pv. phaseolicola PK2. J. Gen. Microbiol. 137 (1991) 2281–2286. [DOI] [PMID: 1770346]
2.	Fukuda, H., Ogawa, T., Tazaki, M., Nagahama, K., Fujii, T., Tanase, S. and Morino, Y. Two reactions are simultaneously catalyzed by a single enzyme: the arginine-dependent simultaneous formation of two products, ethylene and succinate, from 2-oxoglutarate by an enzyme from Pseudomonas syringae. Biochem. Biophys. Res. Commun. 188 (1992) 483–489. [DOI] [PMID: 1445291]
3.	Fukuda, H., Ogawa, T., Ishihara, K., Fujii, T., Nagahama, K., Omata, T., Inoue, Y., Tanase, S. and Morino, Y. Molecular cloning in Escherichia coli, expression, and nucleotide sequence of the gene for the ethylene-forming enzyme of Pseudomonas syringae pv. phaseolicola PK2. Biochem. Biophys. Res. Commun. 188 (1992) 826–832. [DOI] [PMID: 1445325]

[EC 1.13.12.19 created 2011]

1.14.11.34

Transferred entry:

2-oxoglutarate/L-arginine monooxygenase/decarboxylase (succinate-forming). Now EC 1.14.20.7, 2-oxoglutarate/L-arginine monooxygenase/decarboxylase (succinate-forming)

[EC 1.14.11.34 created 2011, deleted 2018]

*EC

1.14.12.19

Accepted name:

3-phenylpropanoate dioxygenase

Reaction:

(1) 3-phenylpropanoate + NADH + H⁺ + O₂ = 3-(cis-5,6-dihydroxycyclohexa-1,3-dien-1-yl)propanoate + NAD⁺
(2) (2E)-3-phenylprop-2-enoate + NADH + H⁺ + O₂ = (2E)-3-(2,3-dihydroxyphenyl)prop-2-enoate + NAD⁺

For diagram of reaction, click here

Glossary:

(2E)-3-phenylprop-2-enoate = trans-cinnamate
(2E)-3-(2,3-dihydroxyphenyl)prop-2-enoate = trans-2,3-dihydroxycinnamate

Other name(s):

HcaA1A2CD; Hca dioxygenase; 3-phenylpropionate dioxygenase

Systematic name:

3-phenylpropanoate,NADH:oxygen oxidoreductase (2,3-hydroxylating)

Comments:

This enzyme catalyses a step in the pathway of phenylpropanoid compounds degradation. It catalyses the insertion of both atoms of molecular oxygen into positions 2 and 3 of the phenyl ring of 3-phenylpropanoate or (2E)-3-phenylprop-2-enoate.

Links to other databases:

References:

1.	Díaz, E., Ferrández, A. and García, J.L. Characterization of the hca cluster encoding the dioxygenolytic pathway for initial catabolism of 3-phenylpropionic acid in Escherichia coli K-12. J. Bacteriol. 180 (1998) 2915–2923. [PMID: 9603882]
2.	Burlingame, R. and Chapman, P.J. Catabolism of phenylpropionic acid and its 3-hydroxy derivative by Escherichia coli. J. Bacteriol. 155 (1983) 113–121. [PMID: 6345502]

[EC 1.14.12.19 created 2005, modified 2011]

1.14.13.3

Transferred entry:

4-hydroxyphenylacetate 3-monooxygenase. Now EC 1.14.14.9, 4-hydroxyphenylacetate 3-monooxygenase.

[EC 1.14.13.3 created 1972, deleted 2011]

1.14.13.131

Accepted name:

dissimilatory dimethyl sulfide monooxygenase

Reaction:

dimethyl sulfide + O₂ + NADH + H⁺ = methanethiol + formaldehyde + NAD⁺ + H₂O

For diagram of dimethyl sulfide catabolism, click here

Other name(s):

dmoAB (gene names); dimethyl sulfide C-monooxygenase; dimethylsulfide monooxygenase (ambiguous); dimethyl sulfide monooxygenase (ambiguous)

Systematic name:

dimethyl sulfide,NADH:oxygen oxidoreductase

Comments:

The enzyme participates exclusively in sulfur dissimilation. It has lower activity with diethyl sulfide and other short-chain alkyl methyl sulfides. Its activity is stimulated by combined addition of FMN, and, after depletion of cations, of Mg²⁺ and Fe²⁺. The enzymes from bacteria of the Hyphomicrobium genus are a two component system that includes an FMN-dependent reductase subunit and a monooxygenase subunit.

Links to other databases:

References:

1.	De Bont, J.A.M., Van Dijken, J.P. and Harder, W. Dimethyl sulphoxide and dimethyl sulphide as a carbon, sulphur and energy source for growth of Hyphomicrobium S. J. Gen. Microbiol. 127 (1981) 315–323.
2.	Boden, R., Borodina, E., Wood, A.P., Kelly, D.P., Murrell, J.C. and Schafer, H. Purification and characterization of dimethylsulfide monooxygenase from Hyphomicrobium sulfonivorans. J. Bacteriol. 193 (2011) 1250–1258. [DOI] [PMID: 21216999]

[EC 1.14.13.131 created 2011]

1.14.13.132

Transferred entry:

squalene monooxygenase. Now EC 1.14.14.17, squalene monooxygenase

[EC 1.14.13.132 created 1961 as EC 1.99.1.13, transferred 1965 to EC 1.14.1.3, part transferred 1972 to EC 1.14.99.7, transferred 2011 to EC 1.14.13.132, deleted 2015]

1.14.13.133

Transferred entry:

pentalenene oxygenase. Now EC 1.14.15.32, pentalenene oxygenase

[EC 1.14.13.133 created 2011, deleted 2018]

1.14.13.134

Transferred entry:

β-amyrin 11-oxidase. Now EC 1.14.14.152, β-amyrin 11-oxidase

[EC 1.14.13.134 created 2011, deleted 2018]

1.14.13.135

Accepted name:

1-hydroxy-2-naphthoate hydroxylase

Reaction:

1-hydroxy-2-naphthoate + NAD(P)H + H⁺ + O₂ = 1,2-dihydroxynaphthalene + NAD(P)⁺ + H₂O + CO₂

Other name(s):

1-hydroxy-2-naphthoic acid hydroxylase

Systematic name:

1-hydroxy-2-naphthoate,NAD(P)H:oxygen oxidoreductase (2-hydroxylating, decarboxylating)

Comments:

The enzyme is involved in the catabolic pathway for the degradation of chrysene in some bacteria [2].

Links to other databases:

References:

1.	Deveryshetty, J. and Phale, P.S. Biodegradation of phenanthrene by Alcaligenes sp. strain PPH: partial purification and characterization of 1-hydroxy-2-naphthoic acid hydroxylase. FEMS Microbiol. Lett. 311 (2010) 93–101. [DOI] [PMID: 20727010]
2.	Nayak, A.S., Sanjeev Kumar, S., Santosh Kumar, M., Anjaneya, O. and Karegoudar, T.B. A catabolic pathway for the degradation of chrysene by Pseudoxanthomonas sp. PNK-04. FEMS Microbiol. Lett. 320 (2011) 128–134. [DOI] [PMID: 21545490]

[EC 1.14.13.135 created 2011]

1.14.13.136

Transferred entry:

2-hydroxyisoflavanone synthase. Now EC 1.14.14.87, 2-hydroxyisoflavanone synthase

[EC 1.14.13.136 created 2011, modified 2013, deleted 2018]

1.14.14.9

Accepted name:

4-hydroxyphenylacetate 3-monooxygenase

Reaction:

4-hydroxyphenylacetate + FADH₂ + O₂ = 3,4-dihydroxyphenylacetate + FAD + H₂O

Other name(s):

p-hydroxyphenylacetate 3-hydroxylase; 4-hydroxyphenylacetic acid-3-hydroxylase; p-hydroxyphenylacetate hydroxylase (FAD); 4 HPA 3-hydroxylase; p-hydroxyphenylacetate 3-hydroxylase (FAD); HpaB

Systematic name:

4-hydroxyphenylacetate,FADH₂:oxygen oxidoreductase (3-hydroxylating)

Comments:

The enzyme from Escherichia coli attacks a broad spectrum of phenolic compounds. The enzyme uses FADH₂ as a substrate rather than a cofactor [4]. FADH₂ is provided by EC 1.5.1.36, flavin reductase (NADH) [5,6].

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 37256-71-6

References:

1.	Adachi, K., Takeda, Y., Senoh, S. and Kita, H. Metabolism of p-hydroxyphenylacetic acid in Pseudomonas ovalis. Biochim. Biophys. Acta 93 (1964) 483–493. [DOI] [PMID: 14263147]
2.	Prieto, M.A., Perez-Aranda, A. and Garcia, J.L. Characterization of an Escherichia coli aromatic hydroxylase with a broad substrate range. J. Bacteriol. 175 (1993) 2162–2167. [DOI] [PMID: 8458860]
3.	Prieto, M.A. and Garcia, J.L. Molecular characterization of 4-hydroxyphenylacetate 3-hydroxylase of Escherichia coli. A two-protein component enzyme. J. Biol. Chem. 269 (1994) 22823–22829. [PMID: 8077235]
4.	Xun, L. and Sandvik, E.R. Characterization of 4-hydroxyphenylacetate 3-hydroxylase (HpaB) of Escherichia coli as a reduced flavin adenine dinucleotide-utilizing monooxygenase. Appl. Environ. Microbiol. 66 (2000) 481–486. [DOI] [PMID: 10653707]
5.	Galan, B., Diaz, E., Prieto, M.A. and Garcia, J.L. Functional analysis of the small component of the 4-hydroxyphenylacetate 3-monooxygenase of Escherichia coli W: a prototype of a new Flavin:NAD(P)H reductase subfamily. J. Bacteriol. 182 (2000) 627–636. [DOI] [PMID: 10633095]
6.	Louie, T.M., Xie, X.S. and Xun, L. Coordinated production and utilization of FADH₂ by NAD(P)H-flavin oxidoreductase and 4-hydroxyphenylacetate 3-monooxygenase. Biochemistry 42 (2003) 7509–7517. [DOI] [PMID: 12809507]

[EC 1.14.14.9 created 1972 as EC 1.14.13.3, transferred 2011 to EC 1.14.14.9]

1.14.14.10

Accepted name:

nitrilotriacetate monooxygenase

Reaction:

nitrilotriacetate + FMNH₂ + H⁺ + O₂ = iminodiacetate + glyoxylate + FMN + H₂O

Systematic name:

nitrilotriacetate,FMNH₂:oxygen oxidoreductase (glyoxylate-forming)

Comments:

Requires Mg²⁺. The enzyme from Aminobacter aminovorans (previously Chelatobacter heintzii) is part of a two component system that also includes EC 1.5.1.42 (FMN reductase), which provides reduced flavin mononucleotide for this enzyme.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG

References:

1.	Uetz, T., Schneider, R., Snozzi, M. and Egli, T. Purification and characterization of a two-component monooxygenase that hydroxylates nitrilotriacetate from "Chelatobacter" strain ATCC 29600. J. Bacteriol. 174 (1992) 1179–1188. [DOI] [PMID: 1735711]
2.	Knobel, H.R., Egli, T. and van der Meer, J.R. Cloning and characterization of the genes encoding nitrilotriacetate monooxygenase of Chelatobacter heintzii ATCC 29600. J. Bacteriol. 178 (1996) 6123–6132. [DOI] [PMID: 8892809]
3.	Xu, Y., Mortimer, M.W., Fisher, T.S., Kahn, M.L., Brockman, F.J. and Xun, L. Cloning, sequencing, and analysis of a gene cluster from Chelatobacter heintzii ATCC 29600 encoding nitrilotriacetate monooxygenase and NADH:flavin mononucleotide oxidoreductase. J. Bacteriol. 179 (1997) 1112–1116. [DOI] [PMID: 9023192]

[EC 1.14.14.10 created 2011]

1.14.14.11

Accepted name:

styrene monooxygenase

Reaction:

styrene + FADH₂ + O₂ = (S)-2-phenyloxirane + FAD + H₂O

Other name(s):

StyA; SMO; NSMOA

Systematic name:

styrene,FADH₂:oxygen oxidoreductase

Comments:

The enzyme catalyses the first step in the aerobic styrene degradation pathway. It forms a two-component system with a reductase (StyB) that utilizes NADH to reduce flavin-adenine dinucleotide, which is then transferred to the oxygenase.

Links to other databases:

References:

1.	Otto, K., Hofstetter, K., Rothlisberger, M., Witholt, B. and Schmid, A. Biochemical characterization of StyAB from Pseudomonas sp. strain VLB120 as a two-component flavin-diffusible monooxygenase. J. Bacteriol. 186 (2004) 5292–5302. [DOI] [PMID: 15292130]
2.	Tischler, D., Kermer, R., Groning, J.A., Kaschabek, S.R., van Berkel, W.J. and Schlomann, M. StyA1 and StyA2B from Rhodococcus opacus 1CP: a multifunctional styrene monooxygenase system. J. Bacteriol. 192 (2010) 5220–5227. [DOI] [PMID: 20675468]

[EC 1.14.14.11 created 2011]

1.14.14.12

Accepted name:

3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione monooxygenase

Reaction:

3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione + FMNH₂ + O₂ = 3,4-dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione + FMN + H₂O

Other name(s):

HsaA

Systematic name:

3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione,FMNH₂:oxygen oxidoreductase

Comments:

This bacterial enzyme participates in the degradation of several steroids, including cholesterol and testosterone. It can use either FADH or FMNH₂ as flavin cofactor. The enzyme forms a two-component system with a reductase (HsaB) that utilizes NADH to reduce the flavin, which is then transferred to the oxygenase subunit.

Links to other databases:

References:

1.	Dresen, C., Lin, L.Y., D'Angelo, I., Tocheva, E.I., Strynadka, N. and Eltis, L.D. A flavin-dependent monooxygenase from Mycobacterium tuberculosis involved in cholesterol catabolism. J. Biol. Chem. 285 (2010) 22264–22275. [DOI] [PMID: 20448045]

[EC 1.14.14.12 created 2011]

1.14.99.7

Transferred entry:

squalene monooxygenase. Transferred to EC 1.14.13.132, squalene monooxygenase.

[EC 1.14.99.7 created 1961 as EC 1.99.1.13, transferred 1965 to EC 1.14.1.3, part transferred 1972 to EC 1.14.99.7 rest to EC 5.4.99.7, deleted 2011]

1.16 Oxidizing metal ions

1.16.9 With a copper protein as acceptor

1.16.9.1

Accepted name:

iron:rusticyanin reductase

Reaction:

Fe(II) + rusticyanin = Fe(III) + reduced rusticyanin

Other name(s):

Cyc2 (ambiguous)

Systematic name:

Fe(II):rusticyanin oxidoreductase

Comments:

Contains c-type heme. The enzyme in Acidithiobacillus ferrooxidans is a component of an electron transfer chain from Fe(II), comprising this enzyme, the copper protein rusticyanin, cytochrome c₄, and cytochrome-c oxidase (EC 7.1.1.9).

Links to other databases:

References:

1.	Blake, R.C., 2nd and Shute, E.A. Respiratory enzymes of Thiobacillus ferrooxidans. Kinetic properties of an acid-stable iron:rusticyanin oxidoreductase. Biochemistry 33 (1994) 9220–9228. [PMID: 8049223]
2.	Appia-Ayme, C., Bengrine, A., Cavazza, C., Giudici-Orticoni, M.T., Bruschi, M., Chippaux, M. and Bonnefoy, V. Characterization and expression of the co-transcribed cyc1 and cyc2 genes encoding the cytochrome c₄ (c₅₅₂) and a high-molecular-mass cytochrome c from Thiobacillus ferrooxidans ATCC 33020. FEMS Microbiol. Lett. 167 (1998) 171–177. [DOI] [PMID: 9809418]
3.	Yarzabal, A., Brasseur, G., Ratouchniak, J., Lund, K., Lemesle-Meunier, D., DeMoss, J.A. and Bonnefoy, V. The high-molecular-weight cytochrome c Cyc2 of Acidithiobacillus ferrooxidans is an outer membrane protein. J. Bacteriol. 184 (2002) 313–317. [DOI] [PMID: 11741873]
4.	Yarzabal, A., Appia-Ayme, C., Ratouchniak, J. and Bonnefoy, V. Regulation of the expression of the Acidithiobacillus ferrooxidans rus operon encoding two cytochromes c, a cytochrome oxidase and rusticyanin. Microbiology 150 (2004) 2113–2123. [DOI] [PMID: 15256554]
5.	Taha, T.M., Kanao, T., Takeuchi, F. and Sugio, T. Reconstitution of iron oxidase from sulfur-grown Acidithiobacillus ferrooxidans. Appl. Environ. Microbiol. 74 (2008) 6808–6810. [DOI] [PMID: 18791023]
6.	Castelle, C., Guiral, M., Malarte, G., Ledgham, F., Leroy, G., Brugna, M. and Giudici-Orticoni, M.T. A new iron-oxidizing/O₂-reducing supercomplex spanning both inner and outer membranes, isolated from the extreme acidophile Acidithiobacillus ferrooxidans. J. Biol. Chem. 283 (2008) 25803–25811. [DOI] [PMID: 18632666]
7.	Quatrini, R., Appia-Ayme, C., Denis, Y., Jedlicki, E., Holmes, D.S. and Bonnefoy, V. Extending the models for iron and sulfur oxidation in the extreme acidophile Acidithiobacillus ferrooxidans. BMC Genomics 10:394 (2009). [DOI] [PMID: 19703284]

[EC 1.16.9.1 created 2011 as EC 1.16.98.1, transferred 2011 to EC 1.16.9.1]

*EC

1.17.1.4

Accepted name:

xanthine dehydrogenase

Reaction:

xanthine + NAD⁺ + H₂O = urate + NADH + H⁺

For diagram of reaction, click here

Glossary:

4-mercuribenzoate = (4-carboxylatophenyl)mercury

Other name(s):

NAD⁺-xanthine dehydrogenase; xanthine-NAD⁺ oxidoreductase; xanthine/NAD⁺ oxidoreductase; xanthine oxidoreductase

Systematic name:

xanthine:NAD⁺ oxidoreductase

Comments:

Acts on a variety of purines and aldehydes, including hypoxanthine. The mammalian enzyme can also convert all-trans retinol to all-trans-retinoate, while the substrate is bound to a retinoid-binding protein [14]. The enzyme from eukaryotes contains [2Fe-2S], FAD and a molybdenum centre. The mammalian enzyme predominantly exists as the NAD-dependent dehydrogenase (EC 1.17.1.4). During purification the enzyme is largely converted to an O₂-dependent form, xanthine oxidase (EC 1.17.3.2). The conversion can be triggered by several mechanisms, including the oxidation of cysteine thiols to form disulfide bonds [2,6,8,15] [which can be catalysed by EC 1.8.4.7, enzyme-thiol transhydrogenase (glutathione-disulfide) in the presence of glutathione disulfide] or limited proteolysis, which results in irreversible conversion. The conversion can also occur in vivo [2,7,15].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9054-84-6

References:

1.	Battelli, M.G. and Lorenzoni, E. Purification and properties of a new glutathione-dependent thiol:disulphide oxidoreductase from rat liver. Biochem. J. 207 (1982) 133–138. [PMID: 6960894]
2.	Della Corte, E. and Stirpe, F. The regulation of rat liver xanthine oxidase. Involvement of thiol groups in the conversion of the enzyme activity from dehydrogenase (type D) into oxidase (type O) and purification of the enzyme. Biochem. J. 126 (1972) 739–745. [PMID: 4342395]
3.	Parzen, S.D. and Fox, A.S. Purification of xanthine dehydrogenase from Drosophila melanogaster. Biochim. Biophys. Acta 92 (1964) 465–471. [PMID: 14264879]
4.	Rajagopalan, K.V. and Handler, P. Purification and properties of chicken liver xanthine dehydrogenase. J. Biol. Chem. 242 (1967) 4097–4107. [PMID: 4294045]
5.	Smith, S.T., Rajagopalan, K.V. and Handler, P. Purification and properties of xanthine dehydroganase from Micrococcus lactilyticus. J. Biol. Chem. 242 (1967) 4108–4117. [PMID: 6061702]
6.	Ikegami, T. and Nishino, T. The presence of desulfo xanthine dehydrogenase in purified and crude enzyme preparations from rat liver. Arch. Biochem. Biophys. 247 (1986) 254–260. [DOI] [PMID: 3459393]
7.	Engerson, T.D., McKelvey, T.G., Rhyne, D.B., Boggio, E.B., Snyder, S.J. and Jones, H.P. Conversion of xanthine dehydrogenase to oxidase in ischemic rat tissues. J. Clin. Invest. 79 (1987) 1564–1570. [DOI] [PMID: 3294898]
8.	Saito, T., Nishino, T. and Tsushima, K. Interconversion between NAD-dependent and O₂-dependent types of rat liver xanthine dehydrogenase and difference in kinetic and redox properties between them. Adv. Exp. Med. Biol. 253B (1989) 179–183. [PMID: 2610112]
9.	Parschat, K., Canne, C., Hüttermann, J., Kappl, R. and Fetzner, S. Xanthine dehydrogenase from Pseudomonas putida 86: specificity, oxidation-reduction potentials of its redox-active centers, and first EPR characterization. Biochim. Biophys. Acta 1544 (2001) 151–165. [DOI] [PMID: 11341925]
10.	Ichida, K., Amaya, Y., Noda, K., Minoshima, S., Hosoya, T., Sakai, O., Shimizu, N. and Nishino, T. Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): structural analysis of the protein and chromosomal location of the gene. Gene 133 (1993) 279–284. [DOI] [PMID: 8224915]
11.	Enroth, C., Eger, B.T., Okamoto, K., Nishino, T., Nishino, T. and Pai, E.F. Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion. Proc. Natl. Acad. Sci. USA 97 (2000) 10723–10728. [DOI] [PMID: 11005854]
12.	Truglio, J.J., Theis, K., Leimkuhler, S., Rappa, R., Rajagopalan, K.V. and Kisker, C. Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus. Structure 10 (2002) 115–125. [DOI] [PMID: 11796116]
13.	Hille, R. The mononuclear molybdenum enzymes. Chem. Rev. 96 (1996) 2757–2816. [DOI] [PMID: 11848841]
14.	Taibi, G., Di Gaudio, F. and Nicotra, C.M. Xanthine dehydrogenase processes retinol to retinoic acid in human mammary epithelial cells. J. Enzyme Inhib. Med. Chem. 23 (2008) 317–327. [DOI] [PMID: 18569334]
15.	Nishino, T., Okamoto, K., Eger, B.T., Pai, E.F. and Nishino, T. Mammalian xanthine oxidoreductase - mechanism of transition from xanthine dehydrogenase to xanthine oxidase. FEBS J. 275 (2008) 3278–3289. [DOI] [PMID: 18513323]

[EC 1.17.1.4 created 1972 as EC 1.2.1.37, transferred 1984 to EC 1.1.1.204, modified 1989, transferred 2004 to EC 1.17.1.4, modified 2011]

1.17.1.7

Transferred entry:

3-oxo-5,6-dehydrosuberyl-CoA semialdehyde dehydrogenase. Now EC 1.2.1.91, 3-oxo-5,6-dehydrosuberyl-CoA semialdehyde dehydrogenase

[EC 1.17.1.7 created 2011, deleted 2014]

*EC

1.17.3.2

Accepted name:

xanthine oxidase

Reaction:

xanthine + H₂O + O₂ = urate + H₂O₂

For diagram of AMP catabolism, click here

Glossary:

4-mercuribenzoate = (4-carboxylatophenyl)mercury

Other name(s):

hypoxanthine oxidase; hypoxanthine:oxygen oxidoreductase; Schardinger enzyme; xanthine oxidoreductase; hypoxanthine-xanthine oxidase; xanthine:O₂ oxidoreductase; xanthine:xanthine oxidase

Systematic name:

xanthine:oxygen oxidoreductase

Comments:

An iron-molybdenum flavoprotein (FAD) containing [2Fe-2S] centres. Also oxidizes hypoxanthine, some other purines and pterins, and aldehydes, but is distinct from EC 1.2.3.1, aldehyde oxidase. Under some conditions the product is mainly superoxide rather than peroxide: RH + H₂O + 2 O₂ = ROH + 2 O₂^.- + 2 H⁺. The mammalian enzyme predominantly exists as an NAD-dependent dehydrogenase (EC 1.17.1.4, xanthine dehydrogenase). During purification the enzyme is largely converted to the O₂-dependent xanthine oxidase form (EC 1.17.3.2). The conversion can be triggered by several mechanisms, including the oxidation of cysteine thiols to form disulfide bonds [4,5,7,10] [which can be catalysed by EC 1.8.4.7, enzyme-thiol transhydrogenase (glutathione-disulfide) in the presence of glutathione disulfide] or limited proteolysis, which results in irreversible conversion. The conversion can also occur in vivo [4,6,10].

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 9002-17-9

References:

1.	Avis, P.G., Bergel, F. and Bray, R.C. Cellular constituents. The chemistry of xanthine oxidase. Part I. The preparation of a crystalline xanthine oxidase from cow's milk. J. Chem. Soc. (Lond.) (1955) 1100–1105.
2.	Battelli, M.G. and Lorenzoni, E. Purification and properties of a new glutathione-dependent thiol:disulphide oxidoreductase from rat liver. Biochem. J. 207 (1982) 133–138. [PMID: 6960894]
3.	Bray, R.C. Xanthine oxidase. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Ed.), The Enzymes, 2nd edn, vol. 7, Academic Press, New York, 1963, pp. 533–556.
4.	Della Corte, E. and Stirpe, F. The regulation of rat liver xanthine oxidase. Involvement of thiol groups in the conversion of the enzyme activity from dehydrogenase (type D) into oxidase (type O) and purification of the enzyme. Biochem. J. 126 (1972) 739–745. [PMID: 4342395]
5.	Ikegami, T. and Nishino, T. The presence of desulfo xanthine dehydrogenase in purified and crude enzyme preparations from rat liver. Arch. Biochem. Biophys. 247 (1986) 254–260. [DOI] [PMID: 3459393]
6.	Engerson, T.D., McKelvey, T.G., Rhyne, D.B., Boggio, E.B., Snyder, S.J. and Jones, H.P. Conversion of xanthine dehydrogenase to oxidase in ischemic rat tissues. J. Clin. Invest. 79 (1987) 1564–1570. [DOI] [PMID: 3294898]
7.	Saito, T., Nishino, T. and Tsushima, K. Interconversion between NAD-dependent and O₂-dependent types of rat liver xanthine dehydrogenase and difference in kinetic and redox properties between them. Adv. Exp. Med. Biol. 253B (1989) 179–183. [PMID: 2610112]
8.	Carpani, G., Racchi, M., Ghezzi, P., Terao, M. and Garattini, E. Purification and characterization of mouse liver xanthine oxidase. Arch. Biochem. Biophys. 279 (1990) 237–241. [DOI] [PMID: 2350174]
9.	Eger, B.T., Okamoto, K., Enroth, C., Sato, M., Nishino, T., Pai, E.F. and Nishino, T. Purification, crystallization and preliminary X-ray diffraction studies of xanthine dehydrogenase and xanthine oxidase isolated from bovine milk. Acta Crystallogr. D Biol. Crystallogr. 56 (2000) 1656–1658. [PMID: 11092937]
10.	Nishino, T., Okamoto, K., Eger, B.T., Pai, E.F. and Nishino, T. Mammalian xanthine oxidoreductase - mechanism of transition from xanthine dehydrogenase to xanthine oxidase. FEBS J. 275 (2008) 3278–3289. [DOI] [PMID: 18513323]

[EC 1.17.3.2 created 1961 as EC 1.2.3.2, transferred 1984 to EC 1.1.3.22, modified 1989, transferred 2004 to EC 1.17.3.2, modified 2011]

1.17.7.2

Accepted name:

7-hydroxymethyl chlorophyll a reductase

Reaction:

chlorophyll a + H₂O + 2 oxidized ferredoxin = 7¹-hydroxychlorophyll a + 2 reduced ferredoxin + 2 H⁺

For diagram of the chlorophyll cycle, click here

Glossary:

7¹-hydroxychlorophyll a = 7-hydroxymethyl-chlorophyll a

Other name(s):

HCAR; 7¹-hydroxychlorophyll-a:ferredoxin oxidoreductase

Systematic name:

chlorophyll-a:ferredoxin oxidoreductase

Comments:

Contains FAD and an iron-sulfur center. This enzyme, which is present in plant chloroplasts, carries out the second step in the conversion of chlorophyll b to chlorophyll a. It similarly reduces chlorophyllide a.

Links to other databases:

References:

1.	Meguro, M., Ito, H., Takabayashi, A., Tanaka, R. and Tanaka, A. Identification of the 7-hydroxymethyl chlorophyll a reductase of the chlorophyll cycle in Arabidopsis. Plant Cell 23 (2011) 3442–3453. [DOI] [PMID: 21934147]

[EC 1.17.7.2 created 2011]

1.20 Acting on phosphorus or arsenic in donors

1.20.2 With a cytochrome as acceptor

1.20.2.1

Accepted name:

arsenate reductase (cytochrome c)

Reaction:

arsenite + H₂O + 2 oxidized cytochrome c = arsenate + 2 reduced cytochrome c + 2 H⁺

Other name(s):

arsenite oxidase (ambiguous)

Systematic name:

arsenite:cytochrome c oxidoreductase

Comments:

A molybdoprotein containing iron-sulfur clusters. Isolated from α-proteobacteria. Unlike EC 1.20.9.1, arsenate reductase (azurin), it does not use azurin as acceptor.

Links to other databases:

References:

1.	vanden Hoven, R.N. and Santini, J.M. Arsenite oxidation by the heterotroph Hydrogenophaga sp. str. NT-14: the arsenite oxidase and its physiological electron acceptor. Biochim. Biophys. Acta 1656 (2004) 148–155. [DOI] [PMID: 15178476]
2.	Santini, J.M., Kappler, U., Ward, S.A., Honeychurch, M.J., vanden Hoven, R.N. and Bernhardt, P.V. The NT-26 cytochrome c₅₅₂ and its role in arsenite oxidation. Biochim. Biophys. Acta 1767 (2007) 189–196. [DOI] [PMID: 17306216]
3.	Branco, R., Francisco, R., Chung, A.P. and Morais, P.V. Identification of an aox system that requires cytochrome c in the highly arsenic-resistant bacterium Ochrobactrum tritici SCII24. Appl. Environ. Microbiol. 75 (2009) 5141–5147. [DOI] [PMID: 19525272]
4.	Lieutaud, A., van Lis, R., Duval, S., Capowiez, L., Muller, D., Lebrun, R., Lignon, S., Fardeau, M.L., Lett, M.C., Nitschke, W. and Schoepp-Cothenet, B. Arsenite oxidase from Ralstonia sp. 22: characterization of the enzyme and its interaction with soluble cytochromes. J. Biol. Chem. 285 (2010) 20433–20441. [DOI] [PMID: 20421652]

[EC 1.20.2.1 created 2011]

1.20 Acting on phosphorus or arsenic in donors

1.20.9 With a copper protein as acceptor

1.20.9.1

Accepted name:

arsenate reductase (azurin)

Reaction:

arsenite + H₂O + 2 oxidized azurin = arsenate + 2 reduced azurin + 2 H⁺

For diagram of arsenate catabolism, click here

Glossary:

Azurin is a blue copper protein found in many bacteria, which undergoes oxidation-reduction between Cu(I) and Cu(II), and transfers single electrons between enzymes.

Other name(s):

arsenite oxidase (ambiguous)

Systematic name:

arsenite:azurin oxidoreductase

Comments:

Contains a molybdopterin centre comprising two molybdopterin guanosine dinucleotide cofactors bound to molybdenum, a [3Fe-4S] cluster and a Rieske-type [2Fe-2S] cluster. Isolated from β-proteobacteria. Also uses a c-type cytochrome or O₂ as acceptors.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 146907-46-2

References:

1.	Anderson, G.L., Williams, J. and Hille, R. The purification and characterization of arsenite oxidase from Alcaligenes faecalis, a molybdenum-containing hydroxylase. J. Biol. Chem. 267 (1992) 23674–23682. [PMID: 1331097]
2.	Ellis, P.J., Conrads, T., Hille, R. and Kuhn, P. Crystal structure of the 100 kDa arsenite oxidase from Alcaligenes faecalis in two crystal forms at 1.64 Å and 2.03 Å. Structure 9 (2001) 125–132. [DOI] [PMID: 11250197]

[EC 1.20.9.1 created 2001 as EC 1.20.98.1, transferred 2011 to EC 1.20.9.1]

1.20.98.1

Transferred entry:

arsenate reductase (azurin). Now EC 1.20.9.1, arsenate reductase (azurin)

[EC 1.20.98.1 created 2001, deleted 2011]

2.1.1.31

Transferred entry:

tRNA (guanine-N¹-)-methyltransferase. Now covered by EC 2.1.1.221 (tRNA (guanine⁹-N¹)-methyltransferase) and EC 2.1.1.228 (tRNA (guanine³⁷-N¹)-methyltransferase).

[EC 2.1.1.31 created 1972, deleted 2011]

2.1.1.32

Transferred entry:

tRNA (guanine-N²-)-methyltransferase. Now covered by EC 2.1.1.213 [tRNA (guanine¹⁰-N²)-dimethyltransferase], EC 2.1.1.214 [tRNA (guanine¹⁰-N²)-monomethyltransferase], EC 2.1.1.215 [tRNA (guanine²⁶-N²/guanine²⁷-N²)-dimethyltransferase] and EC 2.1.1.216 [tRNA (guanine²⁶-N²)-dimethyltransferase]

[EC 2.1.1.32 created 1972, deleted 2011]

*EC

2.1.1.33

Accepted name:

tRNA (guanine⁴⁶-N⁷)-methyltransferase

Reaction:

S-adenosyl-L-methionine + guanine⁴⁶ in tRNA = S-adenosyl-L-homocysteine + N⁷-methylguanine⁴⁶ in tRNA

Other name(s):

Trm8/Trm82; TrmB; tRNA (m⁷G⁴⁶) methyltransferase; transfer ribonucleate guanine 7-methyltransferase; 7-methylguanine transfer ribonucleate methylase; tRNA guanine 7-methyltransferase; N⁷-methylguanine methylase; S-adenosyl-L-methionine:tRNA (guanine-7-N-)-methyltransferase

Systematic name:

S-adenosyl-L-methionine:tRNA (guanine-N⁷)-methyltransferase

Comments:

The enzyme specifically methylates guanine⁴⁶ at N⁷ in tRNA.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 37257-00-4

References:

1.	Aschhoff, H.J., Elten, H., Arnold, H.H., Mahal, G., Kersten, W. and Kersten, H. 7-Methylguanine specific tRNA-methyltransferase from Escherichia coli. Nucleic Acids Res. 3 (1976) 3109–3122. [DOI] [PMID: 794833]
2.	Zegers, I., Gigot, D., van Vliet, F., Tricot, C., Aymerich, S., Bujnicki, J.M., Kosinski, J. and Droogmans, L. Crystal structure of Bacillus subtilis TrmB, the tRNA (m⁷G⁴⁶) methyltransferase. Nucleic Acids Res. 34 (2006) 1925–1934. [DOI] [PMID: 16600901]
3.	Purta, E., van Vliet, F., Tricot, C., De Bie, L.G., Feder, M., Skowronek, K., Droogmans, L. and Bujnicki, J.M. Sequence-structure-function relationships of a tRNA (m⁷G⁴⁶) methyltransferase studied by homology modeling and site-directed mutagenesis. Proteins 59 (2005) 482–488. [DOI] [PMID: 15789416]
4.	Liu, Q., Gao, Y., Yang, W., Zhou, H., Gao, Y., Zhang, X., Teng, M. and Niu, L. Crystallization and preliminary crystallographic analysis of tRNA (m⁷G46) methyltransferase from Escherichia coli. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 64 (2008) 743–745. [DOI] [PMID: 18678947]
5.	Alexandrov, A., Martzen, M.R. and Phizicky, E.M. Two proteins that form a complex are required for 7-methylguanosine modification of yeast tRNA. RNA 8 (2002) 1253–1266. [PMID: 12403464]

[EC 2.1.1.33 created 1972, modified 2011]

*EC

2.1.1.35

Accepted name:

tRNA (uracil⁵⁴-C⁵)-methyltransferase

Reaction:

S-adenosyl-L-methionine + uracil⁵⁴ in tRNA = S-adenosyl-L-homocysteine + 5-methyluracil⁵⁴ in tRNA

Other name(s):

transfer RNA uracil⁵⁴ 5-methyltransferase; transfer RNA uracil⁵⁴ methylase; tRNA uracil⁵⁴ 5-methyltransferase; m⁵U⁵⁴-methyltransferase; tRNA:m⁵U⁵⁴-methyltransferase; RUMT; TrmA; 5-methyluridine⁵⁴ tRNA methyltransferase; tRNA(uracil-54,C⁵)-methyltransferase; Trm2; tRNA(m⁵U⁵⁴)methyltransferase

Systematic name:

S-adenosyl-L-methionine:tRNA (uracil⁵⁴-C⁵)-methyltransferase

Comments:

Unlike this enzyme, EC 2.1.1.74 (methylenetetrahydrofolate—tRNA-(uracil⁵⁴-C⁵)-methyltransferase (FADH₂-oxidizing)), uses 5,10-methylenetetrahydrofolate and FADH₂ to supply the atoms for methylation of U⁵⁴ [4].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 37257-02-6

References:

1.	Björk, G.R. and Svensson, I. Studies on microbial RNA. Fractionation of tRNA methylases from Saccharomyces cerevisiae. Eur. J. Biochem. 9 (1969) 207–215. [DOI] [PMID: 4896260]
2.	Greenberg, R. and Dudock, B. Isolation and characterization of m5U-methyltransferase from Escherichia coli. J. Biol. Chem. 255 (1980) 8296–8302. [PMID: 6997293]
3.	Hurwitz, J., Gold, M. and Anders, M. The enzymatic methylation of ribonucleic acid and deoxyribonucleic acid. 3. Purification of soluble ribonucleic acid-methylating enzymes. J. Biol. Chem. 239 (1964) 3462–3473. [PMID: 14245404]
4.	Delk, A.S., Nagle, D.P., Jr. and Rabinowitz, J.C. Methylenetetrahydrofolate-dependent biosynthesis of ribothymidine in transfer RNA of Streptococcus faecalis. Evidence for reduction of the 1-carbon unit by FADH₂. J. Biol. Chem. 255 (1980) 4387–4390. [PMID: 6768721]
5.	Kealey, J.T., Gu, X. and Santi, D.V. Enzymatic mechanism of tRNA (m⁵U⁵⁴)methyltransferase. Biochimie 76 (1994) 1133–1142. [DOI] [PMID: 7748948]
6.	Gu, X., Ivanetich, K.M. and Santi, D.V. Recognition of the T-arm of tRNA by tRNA (m⁵U54)-methyltransferase is not sequence specific. Biochemistry 35 (1996) 11652–11659. [DOI] [PMID: 8794745]
7.	Becker, H.F., Motorin, Y., Sissler, M., Florentz, C. and Grosjean, H. Major identity determinants for enzymatic formation of ribothymidine and pseudouridine in the TΨ-loop of yeast tRNAs. J. Mol. Biol. 274 (1997) 505–518. [DOI] [PMID: 9417931]
8.	Walbott, H., Leulliot, N., Grosjean, H. and Golinelli-Pimpaneau, B. The crystal structure of Pyrococcus abyssi tRNA (uracil-54, C⁵)-methyltransferase provides insights into its tRNA specificity. Nucleic Acids Res. 36 (2008) 4929–4940. [DOI] [PMID: 18653523]

[EC 2.1.1.35 created 1972, modified 2011]

2.1.1.36

Transferred entry:

tRNA (adenine-N¹-)-methyltransferase. Now covered by EC 2.1.1.217 (tRNA (adenine²²-N¹)-methyltransferase), EC 2.1.1.218 (tRNA (adenine⁹-N¹)-methyltransferase), EC 2.1.1.219 (tRNA (adenine⁵⁷-N¹/adenine⁵⁸-N¹)-methyltransferase), EC 2.1.1.220 (tRNA (adenine⁵⁸-N¹)-methyltransferase).

[EC 2.1.1.36 created 1972, deleted 2011]

*EC

2.1.1.42

Accepted name:

flavone 3′-O-methyltransferase

Reaction:

S-adenosyl-L-methionine + 3′-hydroxyflavone = S-adenosyl-L-homocysteine + 3′-methoxyflavone

For diagram of luteolin biosynthesis click here

Other name(s):

o-dihydric phenol methyltransferase; luteolin methyltransferase; luteolin 3′-O-methyltransferase; o-diphenol m-O-methyltransferase; o-dihydric phenol meta-O-methyltransferase; S-adenosylmethionine:flavone/flavonol 3′-O-methyltransferase; quercetin 3′-O-methyltransferase

Systematic name:

S-adenosyl-L-methionine:3′-hydroxyflavone 3′-O-methyltransferase

Comments:

The enzyme prefers flavones with vicinal 3′,4′-dihydroxyl groups.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 37205-55-3

References:

1.	Ebel, J., Hahlbrock, K. and Grisebach, H. Purification and properties of an o-dihydricphenol meta-O-methyltransferase from cell suspension cultures of parsley and its relation to flavonoid biosynthesis. Biochim. Biophys. Acta 268 (1972) 313–326. [DOI] [PMID: 5026305]
2.	Muzac, I., Wang, J., Anzellotti, D., Zhang, H. and Ibrahim, R.K. Functional expression of an Arabidopsis cDNA clone encoding a flavonol 3′-O-methyltransferase and characterization of the gene product. Arch. Biochem. Biophys. 375 (2000) 385–388. [DOI] [PMID: 10700397]
3.	Poulton, J.E., Hahlbrock, K. and Grisebach, H. O-Methylation of flavonoid substrates by a partially purified enzyme from soybean cell suspension cultures. Arch. Biochem. Biophys. 180 (1977) 543–549. [DOI] [PMID: 18099]
4.	Kim, B.G., Lee, H.J., Park, Y., Lim, Y. and Ahn, J.H. Characterization of an O-methyltransferase from soybean. Plant Physiol. Biochem. 44 (2006) 236–241. [DOI] [PMID: 16777424]
5.	Lee, Y.J., Kim, B.G., Chong, Y., Lim, Y. and Ahn, J.H. Cation dependent O-methyltransferases from rice. Planta 227 (2008) 641–647. [DOI] [PMID: 17943312]

[EC 2.1.1.42 created 1976, modified 2011]

*EC

2.1.1.46

Accepted name:

isoflavone 4′-O-methyltransferase

Reaction:

S-adenosyl-L-methionine + a 4′-hydroxyisoflavone = S-adenosyl-L-homocysteine + a 4′-methoxyisoflavone

For diagram of the biosynthesis of biochanin A, click here and for diagram of the biosynthesis of formononetin and derivatives, click here

Other name(s):

4′-hydroxyisoflavone methyltransferase; isoflavone methyltransferase; isoflavone O-methyltransferase

Systematic name:

S-adenosyl-L-methionine:4′-hydroxyisoflavone 4′-O-methyltransferase

Comments:

Requires Mg²⁺ for activity. The enzyme catalyses the methylation of daidzein and genistein. It does not methylate naringenin, apigenin, luteolin or kaempferol.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 55071-80-2

References:

1.	Wengenmayer, H., Ebel, J. and Grisebach, H. Purification and properties of a S-adenosylmethionine: isoflavone 4′-O-methyltransferase from cell suspension cultures of Cicer arietinum L. Eur. J. Biochem. 50 (1974) 135–143. [DOI] [PMID: 4452353]

[EC 2.1.1.46 created 1976, modified 2011]

*EC

2.1.1.74

Accepted name:

methylenetetrahydrofolate—tRNA-(uracil⁵⁴-C⁵)-methyltransferase [NAD(P)H-oxidizing]

Reaction:

5,10-methylenetetrahydrofolate + uracil⁵⁴ in tRNA + NAD(P)H + H⁺ = tetrahydrofolate + 5-methyluracil⁵⁴ in tRNA + NAD(P)⁺

Glossary:

Ψ = pseudouridine
T = ribothymidine = 5-methyluridine

Other name(s):

folate-dependent ribothymidyl synthase; methylenetetrahydrofolate-transfer ribonucleate uracil 5-methyltransferase; 5,10-methylenetetrahydrofolate:tRNA-UΨC (uracil-5-)-methyl-transferase; 5,10-methylenetetrahydrofolate:tRNA (uracil-5-)-methyl-transferase; TrmFO; folate/FAD-dependent tRNA T54 methyltransferase; methylenetetrahydrofolate—tRNA-(uracil⁵⁴-C⁵)-methyltransferase (FADH₂-oxidizing)

Systematic name:

5,10-methylenetetrahydrofolate:tRNA (uracil⁵⁴-C⁵)-methyltransferase

Comments:

A flavoprotein (FAD). Up to 25% of the bases in mature tRNA are post-translationally modified or hypermodified. One almost universal post-translational modification is the conversion of U⁵⁴ into ribothymidine in the TΨC loop, and this modification is found in most species studied to date [2]. Unlike this enzyme, which uses 5,10-methylenetetrahydrofolate and NAD(P)H to supply the atoms for methylation of U⁵⁴, EC 2.1.1.35, tRNA (uracil⁵⁴-C⁵)-methyltransferase, uses S-adenosyl-L-methionine.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 56831-74-4

References:

1.	Delk, A.S., Nagle, D.P., Jr. and Rabinowitz, J.C. Methylenetetrahydrofolate-dependent biosynthesis of ribothymidine in transfer RNA of Streptococcus faecalis. Evidence for reduction of the 1-carbon unit by FADH₂. J. Biol. Chem. 255 (1980) 4387–4390. [PMID: 6768721]
2.	Becker, H.F., Motorin, Y., Sissler, M., Florentz, C. and Grosjean, H. Major identity determinants for enzymatic formation of ribothymidine and pseudouridine in the TΨ-loop of yeast tRNAs. J. Mol. Biol. 274 (1997) 505–518. [DOI] [PMID: 9417931]
3.	Nishimasu, H., Ishitani, R., Yamashita, K., Iwashita, C., Hirata, A., Hori, H. and Nureki, O. Atomic structure of a folate/FAD-dependent tRNA T54 methyltransferase. Proc. Natl. Acad. Sci. USA 106 (2009) 8180–8185. [DOI] [PMID: 19416846]
4.	Yamagami, R., Yamashita, K., Nishimasu, H., Tomikawa, C., Ochi, A., Iwashita, C., Hirata, A., Ishitani, R., Nureki, O. and Hori, H. The tRNA recognition mechanism of folate/FAD-dependent tRNA methyltransferase (TrmFO). J. Biol. Chem. 287 (2012) 42480–42494. [PMID: 23095745]

[EC 2.1.1.74 created 1983 as EC 2.1.2.12, transferred 1984 to EC 2.1.1.74, modified 2011, modified 2019]

*EC

2.1.1.192

Accepted name:

23S rRNA (adenine²⁵⁰³-C²)-methyltransferase

Reaction:

(1) 2 S-adenosyl-L-methionine + adenine²⁵⁰³ in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5′-deoxyadenosine + 2-methyladenine²⁵⁰³ in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
(2) 2 S-adenosyl-L-methionine + adenine³⁷ in tRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5′-deoxyadenosine + 2-methyladenine³⁷ in tRNA + 2 oxidized [2Fe-2S] ferredoxin

Other name(s):

RlmN; YfgB; Cfr

Systematic name:

S-adenosyl-L-methionine:23S rRNA (adenine²⁵⁰³-C²)-methyltransferase

Comments:

Contains an [4Fe-4S] cluster [2]. This enzyme is a member of the ’AdoMet radical’ (radical SAM) family. S-Adenosyl-L-methionine acts as both a radical generator and as the source of the appended methyl group. RlmN first transfers an CH₂ group to a conserved cysteine (Cys³⁵⁵ in Escherichia coli) [6], the generated radical from a second S-adenosyl-L-methionine then attacks the methyl group, exctracting a hydrogen. The formed radical forms a covalent intermediate with the adenine group of the tRNA [9]. RlmN is an endogenous enzyme used by the cell to refine functions of the ribosome in protein synthesis [2]. The enzyme methylates adenosine by a radical mechanism with CH₂ from the S-adenosyl-L-methionine and retention of the hydrogen at C-2 of adenosine²⁵⁰³ of 23S rRNA. It will also methylate 8-methyladenosine²⁵⁰³ of 23S rRNA. cf. EC 2.1.1.224 [23S rRNA (adenine²⁵⁰³-C⁸)-methyltransferase].

Links to other databases:

References:

1.	Toh, S.M., Xiong, L., Bae, T. and Mankin, A.S. The methyltransferase YfgB/RlmN is responsible for modification of adenosine 2503 in 23S rRNA. RNA 14 (2008) 98–106. [DOI] [PMID: 18025251]
2.	Yan, F., LaMarre, J.M., Röhrich, R., Wiesner, J., Jomaa, H., Mankin, A.S. and Fujimori, D.G. RlmN and Cfr are radical SAM enzymes involved in methylation of ribosomal RNA. J. Am. Chem. Soc. 132 (2010) 3953–3964. [DOI] [PMID: 20184321]
3.	Yan, F. and Fujimori, D.G. RNA methylation by radical SAM enzymes RlmN and Cfr proceeds via methylene transfer and hydride shift. Proc. Natl. Acad. Sci. USA 108 (2011) 3930–3934. [DOI] [PMID: 21368151]
4.	Grove, T.L., Benner, J.S., Radle, M.I., Ahlum, J.H., Landgraf, B.J., Krebs, C. and Booker, S.J. A radically different mechanism for S-adenosylmethionine-dependent methyltransferases. Science 332 (2011) 604–607. [DOI] [PMID: 21415317]
5.	Boal, A.K., Grove, T.L., McLaughlin, M.I., Yennawar, N.H., Booker, S.J. and Rosenzweig, A.C. Structural basis for methyl transfer by a radical SAM enzyme. Science 332 (2011) 1089–1092. [DOI] [PMID: 21527678]
6.	Grove, T.L., Radle, M.I., Krebs, C. and Booker, S.J. Cfr and RlmN contain a single [4Fe-4S] cluster, which directs two distinct reactivities for S-adenosylmethionine: methyl transfer by S_N2 displacement and radical generation. J. Am. Chem. Soc. 133 (2011) 19586–19589. [DOI] [PMID: 21916495]
7.	McCusker, K.P., Medzihradszky, K.F., Shiver, A.L., Nichols, R.J., Yan, F., Maltby, D.A., Gross, C.A. and Fujimori, D.G. Covalent intermediate in the catalytic mechanism of the radical S-adenosyl-L-methionine methyl synthase RlmN trapped by mutagenesis. J. Am. Chem. Soc. 134 (2012) 18074–18081. [DOI] [PMID: 23088750]
8.	Benitez-Paez, A., Villarroya, M. and Armengod, M.E. The Escherichia coli RlmN methyltransferase is a dual-specificity enzyme that modifies both rRNA and tRNA and controls translational accuracy. RNA 18 (2012) 1783–1795. [DOI] [PMID: 22891362]
9.	Silakov, A., Grove, T.L., Radle, M.I., Bauerle, M.R., Green, M.T., Rosenzweig, A.C., Boal, A.K. and Booker, S.J. Characterization of a cross-linked protein-nucleic acid substrate radical in the reaction catalyzed by RlmN. J. Am. Chem. Soc. 136 (2014) 8221–8228. [DOI] [PMID: 24806349]

[EC 2.1.1.192 created 2010, modified 2011, modified 2014]

2.1.1.194

Deleted entry:

23S rRNA (adenine²⁵⁰³-C²,C⁸)-dimethyltransferase. A mixture of EC 2.1.1.192 (23S rRNA (adenine²⁵⁰³-C²)-methyltransferase) and EC 2.1.1.224 (23S rRNA (adenine²⁵⁰³-C⁸)-methyltransferase)

[EC 2.1.1.194 created 2010, deleted 2011]

2.1.1.211

Accepted name:

tRNA^Ser (uridine⁴⁴-2′-O)-methyltransferase

Reaction:

S-adenosyl-L-methionine + uridine⁴⁴ in tRNA^Ser = S-adenosyl-L-homocysteine + 2′-O-methyluridine⁴⁴ in tRNA^Ser

Other name(s):

TRM44

Systematic name:

S-adenosyl-L-methionine:tRNA^Ser (uridine⁴⁴-2′-O)-methyltransferase

Comments:

The 2′-O-methylation of uridine⁴⁴ contributes to stability of tRNA^Ser(CGA).

Links to other databases:

References:

1.	Kotelawala, L., Grayhack, E.J. and Phizicky, E.M. Identification of yeast tRNA Um44 2′-O-methyltransferase (Trm44) and demonstration of a Trm44 role in sustaining levels of specific tRNA^Ser species. RNA 14 (2008) 158–169. [DOI] [PMID: 18025252]

[EC 2.1.1.211 created 2011]

2.1.1.212

Accepted name:

2,7,4′-trihydroxyisoflavanone 4′-O-methyltransferase

Reaction:

S-adenosyl-L-methionine + 2,4′,7-trihydroxyisoflavanone = S-adenosyl-L-homocysteine + 2,7-dihydroxy-4′-methoxyisoflavanone

For diagram of daidzein biosynthesis, click here

Other name(s):

SAM:2,7,4′-trihydroxyisoflavanone 4′-O-methyltransferase; HI4′OMT; HMM1; MtIOMT5; S-adenosyl-L-methionine:2,7,4′-trihydroxyisoflavanone 4′-O-methyltransferase

Systematic name:

S-adenosyl-L-methionine:2,4′,7-trihydroxyisoflavanone 4′-O-methyltransferase

Comments:

Specifically methylates 2,4′,7-trihydroxyisoflavanone on the 4′-position. No activity with isoflavones [2]. The enzyme is involved in formononetin biosynthesis in legumes [1]. The protein from pea (Pisum sativum) also methylates (+)-6a-hydroxymaackiain at the 3-position (cf. EC 2.1.1.270, (+)-6a-hydroxymaackiain 3-O-methyltransferase) [4].

Links to other databases:

References:

1.	Akashi, T., Sawada, Y., Shimada, N., Sakurai, N., Aoki, T. and Ayabe, S. cDNA cloning and biochemical characterization of S-adenosyl-L-methionine: 2,7,4′-trihydroxyisoflavanone 4′-O-methyltransferase, a critical enzyme of the legume isoflavonoid phytoalexin pathway. Plant Cell Physiol. 44 (2003) 103–112. [PMID: 12610212]
2.	Deavours, B.E., Liu, C.J., Naoumkina, M.A., Tang, Y., Farag, M.A., Sumner, L.W., Noel, J.P. and Dixon, R.A. Functional analysis of members of the isoflavone and isoflavanone O-methyltransferase enzyme families from the model legume Medicago truncatula. Plant Mol. Biol. 62 (2006) 715–733. [DOI] [PMID: 17001495]
3.	Liu, C.J., Deavours, B.E., Richard, S.B., Ferrer, J.L., Blount, J.W., Huhman, D., Dixon, R.A. and Noel, J.P. Structural basis for dual functionality of isoflavonoid O-methyltransferases in the evolution of plant defense responses. Plant Cell 18 (2006) 3656–3669. [DOI] [PMID: 17172354]
4.	Akashi, T., VanEtten, H.D., Sawada, Y., Wasmann, C.C., Uchiyama, H. and Ayabe, S. Catalytic specificity of pea O-methyltransferases suggests gene duplication for (+)-pisatin biosynthesis. Phytochemistry 67 (2006) 2525–2530. [DOI] [PMID: 17067644]

[EC 2.1.1.212 created 2011]

2.1.1.213

Accepted name:

tRNA (guanine¹⁰-N²)-dimethyltransferase

Reaction:

2 S-adenosyl-L-methionine + guanine¹⁰ in tRNA = 2 S-adenosyl-L-homocysteine + N²-dimethylguanine¹⁰ in tRNA (overall reaction)
(1a) S-adenosyl-L-methionine + guanine¹⁰ in tRNA = S-adenosyl-L-homocysteine + N²-methylguanine¹⁰ in tRNA
(1b) S-adenosyl-L-methionine + N²-methylguanine¹⁰ in tRNA = S-adenosyl-L-homocysteine + N²-dimethylguanine¹⁰ in tRNA

Other name(s):

PAB1283; N(2),N(2)-dimethylguanosine tRNA methyltransferase; Trm-G10; PabTrm-G10; PabTrm-m2 2G10 enzyme

Systematic name:

S-adenosyl-L-methionine:tRNA (guanine¹⁰-N²)-dimethyltransferase

Links to other databases:

References:

Armengaud, J., Urbonavicius, J., Fernandez, B., Chaussinand, G., Bujnicki, J.M. and Grosjean, H. N²-Methylation of guanosine at position 10 in tRNA is catalyzed by a THUMP domain-containing, S-adenosylmethionine-dependent methyltransferase, conserved in Archaea and Eukaryota. J. Biol. Chem. 279 (2004) 37142–37152. [DOI] [PMID: 15210688]

[EC 2.1.1.213 created 2011 (EC 2.1.1.32 created 1972, part transferred 2011 to EC 2.1.1.213)]

2.1.1.214

Accepted name:

tRNA (guanine¹⁰-N²)-methyltransferase

Reaction:

S-adenosyl-L-methionine + guanine¹⁰ in tRNA = S-adenosyl-L-homocysteine + N²-methylguanine¹⁰ in tRNA

Other name(s):

(m²G¹⁰) methyltransferase; Trm11-Trm112 complex

Systematic name:

S-adenosyl-L-methionine:tRNA (guanine¹⁰-N²)-methyltransferase

Comments:

In contrast to the archaeal enzyme tRNA (guanine¹⁰-N²)-dimethyltransferase (EC 2.1.1.213), tRNA (guanine¹⁰-N²)-methyltransferase from yeast does not catalyse the methylation from N²-methylguanine¹⁰ to N²-dimethylguanine¹⁰ in tRNA.

Links to other databases:

References:

1.	Purushothaman, S.K., Bujnicki, J.M., Grosjean, H. and Lapeyre, B. Trm11p and Trm112p are both required for the formation of 2-methylguanosine at position 10 in yeast tRNA. Mol. Cell Biol. 25 (2005) 4359–4370. [DOI] [PMID: 15899842]

[EC 2.1.1.214 created 2011 (EC 2.1.1.32 created 1972, part transferred 2011 to EC 2.1.1.214)]

2.1.1.215

Accepted name:

tRNA (guanine²⁶-N²/guanine²⁷-N²)-dimethyltransferase

Reaction:

4 S-adenosyl-L-methionine + guanine²⁶/guanine²⁷ in tRNA = 4 S-adenosyl-L-homocysteine + N²-dimethylguanine²⁶/N²-dimethylguanine²⁷ in tRNA

Other name(s):

Trm1 (ambiguous); tRNA (N²,N²-guanine)-dimethyltransferase; tRNA (m2(2G26) methyltransferase; Trm1[tRNA (m2(2)G26) methyltransferase]

Systematic name:

S-adenosyl-L-methionine:tRNA (guanine²⁶-N²/guanine²⁷-N²)-dimethyltransferase

Comments:

The enzyme from Aquifex aeolicus is similar to the TRM1 methyltransferases of archaea and eukarya (see EC 2.1.1.216, tRNA (guanine²⁶-N²)-dimethyltransferase). However, it catalyses the double methylation of guanines at both positions 26 and 27 of tRNA.

Links to other databases:

References:

Awai, T., Kimura, S., Tomikawa, C., Ochi, A., Ihsanawati, Bessho, Y., Yokoyama, S., Ohno, S., Nishikawa, K., Yokogawa, T., Suzuki, T. and Hori, H. Aquifex aeolicus tRNA (N²,N²-guanine)-dimethyltransferase (Trm1) catalyzes transfer of methyl groups not only to guanine 26 but also to guanine 27 in tRNA. J. Biol. Chem. 284 (2009) 20467–20478. [DOI] [PMID: 19491098]

[EC 2.1.1.215 created 2011 (EC 2.1.1.32 created 1972, part transferred 2011 to EC 2.1.1.215)]

2.1.1.216

Accepted name:

tRNA (guanine²⁶-N²)-dimethyltransferase

Reaction:

2 S-adenosyl-L-methionine + guanine²⁶ in tRNA = 2 S-adenosyl-L-homocysteine + N²-dimethylguanine²⁶ in tRNA

Other name(s):

Trm1p; TRM1; tRNA (m²₂G₂₆)dimethyltransferase

Systematic name:

S-adenosyl-L-methionine:tRNA (guanine²⁶-N²)-dimethyltransferase

Comments:

The enzyme dissociates from its tRNA substrate between the two consecutive methylation reactions. In contrast to EC 2.1.1.215, tRNA (guanine²⁶-N²/guanine²⁷-N²)-dimethyltransferase, this enzyme does not catalyse the methylation of guanine²⁷ in tRNA.

Links to other databases:

References:

1.	Constantinesco, F., Motorin, Y. and Grosjean, H. Characterisation and enzymatic properties of tRNA(guanine²⁶, N²,N²-dimethyltransferase (Trm1p) from Pyrococcus furiosus. J. Mol. Biol. 291 (1999) 375–392. [DOI] [PMID: 10438627]
2.	Constantinesco, F., Benachenhou, N., Motorin, Y. and Grosjean, H. The tRNA(guanine-26,N²-N²) methyltransferase (Trm1) from the hyperthermophilic archaeon Pyrococcus furiosus: cloning, sequencing of the gene and its expression in Escherichia coli. Nucleic Acids Res. 26 (1998) 3753–3761. [DOI] [PMID: 9685492]
3.	Liu, J., Liu, J. and Straby, K.B. Point and deletion mutations eliminate one or both methyl group transfers catalysed by the yeast TRM1 encoded tRNA (m²₂G₂₆)dimethyltransferase. Nucleic Acids Res. 26 (1998) 5102–5108. [DOI] [PMID: 9801306]
4.	Liu, J., Zhou, G.Q. and Straby, K.B. Caenorhabditis elegans ZC376.5 encodes a tRNA (m²₂G₂₆)dimethyltransferance in which ²⁴⁶arginine is important for the enzyme activity. Gene 226 (1999) 73–81. [DOI] [PMID: 10048958]

[EC 2.1.1.216 created 2011 (EC 2.1.1.32 created 1972, part transferred 2011 to EC 2.1.1.216)]

2.1.1.217

Accepted name:

tRNA (adenine²²-N¹)-methyltransferase

Reaction:

S-adenosyl-L-methionine + adenine²² in tRNA = S-adenosyl-L-homocysteine + N¹-methyladenine²² in tRNA

Other name(s):

TrmK; YqfN; Sp1610 (gene name); tRNA: m¹A²² methyltransferase

Systematic name:

S-adenosyl-L-methionine:tRNA (adenine²²-N¹)-methyltransferase

Comments:

The enzyme specifically methylates adenine²² in tRNA.

Links to other databases:

References:

1.	Ta, H.M. and Kim, K.K. Crystal structure of Streptococcus pneumoniae Sp1610, a putative tRNA methyltransferase, in complex with S-adenosyl-L-methionine. Protein Sci. 19 (2010) 617–624. [DOI] [PMID: 20052680]
2.	Roovers, M., Kaminska, K.H., Tkaczuk, K.L., Gigot, D., Droogmans, L. and Bujnicki, J.M. The YqfN protein of Bacillus subtilis is the tRNA: m¹A²² methyltransferase (TrmK). Nucleic Acids Res. 36 (2008) 3252–3262. [DOI] [PMID: 18420655]

[EC 2.1.1.217 created 2011 (EC 2.1.1.36 created 1972, part transferred 2011 to EC 2.1.1.217)]

2.1.1.218

Accepted name:

tRNA (adenine⁹-N¹)-methyltransferase

Reaction:

S-adenosyl-L-methionine + adenine⁹ in tRNA = S-adenosyl-L-homocysteine + N¹-methyladenine⁹ in tRNA

Other name(s):

Trm10p (ambiguous); tRNA(m¹G⁹/m¹A⁹)-methyltransferase; tRNA(m¹G⁹/m¹A⁹)MTase; TK0422p (gene name); tRNA m¹A⁹-methyltransferase; tRNA m¹A⁹ Mtase

Systematic name:

S-adenosyl-L-methionine:tRNA (adenine⁹-N¹)-methyltransferase

Comments:

The enzyme from Sulfolobus acidocaldarius specifically methylates adenine⁹ in tRNA [1]. The bifunctional enzyme from Thermococcus kodakaraensis also catalyses the methylation of guanine⁹ in tRNA (cf. EC 2.1.1.221, tRNA (guanine⁹-N¹)-methyltransferase).

Links to other databases:

References:

1.	Kempenaers, M., Roovers, M., Oudjama, Y., Tkaczuk, K.L., Bujnicki, J.M. and Droogmans, L. New archaeal methyltransferases forming 1-methyladenosine or 1-methyladenosine and 1-methylguanosine at position 9 of tRNA. Nucleic Acids Res. 38 (2010) 6533–6543. [DOI] [PMID: 20525789]

[EC 2.1.1.218 created 2011 (EC 2.1.1.36 created 1972, part transferred 2011 to EC 2.1.1.218)]

2.1.1.219

Accepted name:

tRNA (adenine⁵⁷-N¹/adenine⁵⁸-N¹)-methyltransferase

Reaction:

2 S-adenosyl-L-methionine + adenine⁵⁷/adenine⁵⁸ in tRNA = 2 S-adenosyl-L-homocysteine + N¹-methyladenine⁵⁷/N¹-methyladenine⁵⁸ in tRNA

Other name(s):

TrmI; _PabTrmI; _AqTrmI; _MtTrmI

Systematic name:

S-adenosyl-L-methionine:tRNA (adenine⁵⁷/adenine⁵⁸-N¹)-methyltransferase

Comments:

The enzyme catalyses the formation of N¹-methyladenine at two adjacent positions (57 and 58) in the T-loop of certain tRNAs (e.g. tRNA^Asp). Methyladenosine at position 57 is an obligatory intermediate for the synthesis of methylinosine, which is commonly found at position 57 of archaeal tRNAs.

Links to other databases:

References:

1.	Roovers, M., Wouters, J., Bujnicki, J.M., Tricot, C., Stalon, V., Grosjean, H. and Droogmans, L. A primordial RNA modification enzyme: the case of tRNA (m¹A) methyltransferase. Nucleic Acids Res. 32 (2004) 465–476. [DOI] [PMID: 14739239]
2.	Guelorget, A., Roovers, M., Guerineau, V., Barbey, C., Li, X. and Golinelli-Pimpaneau, B. Insights into the hyperthermostability and unusual region-specificity of archaeal Pyrococcus abyssi tRNA m¹A^57/58 methyltransferase. Nucleic Acids Res. 38 (2010) 6206–6218. [DOI] [PMID: 20483913]

[EC 2.1.1.219 created 2011 (EC 2.1.1.36 created 1972, part transferred 2011 to EC 2.1.1.219)]

2.1.1.220

Accepted name:

tRNA (adenine⁵⁸-N¹)-methyltransferase

Reaction:

S-adenosyl-L-methionine + adenine⁵⁸ in tRNA = S-adenosyl-L-homocysteine + N¹-methyladenine⁵⁸ in tRNA

Other name(s):

tRNA m¹A⁵⁸ methyltransferase; tRNA (m¹A⁵⁸) methyltransferase; TrmI; tRNA (m¹A⁵⁸) Mtase; Rv2118cp; Gcd10p-Gcd14p; Trm61p-Trm6p

Systematic name:

S-adenosyl-L-methionine:tRNA (adenine⁵⁸-N¹)-methyltransferase

Comments:

The enzyme specifically methylates adenine⁵⁸ in tRNA. The methylation of A58 is critical for maintaining the stability of initiator tRNA^Met in yeast [3].

Links to other databases:

References:

1.	Droogmans, L., Roovers, M., Bujnicki, J.M., Tricot, C., Hartsch, T., Stalon, V. and Grosjean, H. Cloning and characterization of tRNA (m¹A⁵⁸) methyltransferase (TrmI) from Thermus thermophilus HB27, a protein required for cell growth at extreme temperatures. Nucleic Acids Res. 31 (2003) 2148–2156. [PMID: 12682365]
2.	Varshney, U., Ramesh, V., Madabushi, A., Gaur, R., Subramanya, H.S. and RajBhandary, U.L. Mycobacterium tuberculosis Rv2118c codes for a single-component homotetrameric m¹A⁵⁸ tRNA methyltransferase. Nucleic Acids Res. 32 (2004) 1018–1027. [DOI] [PMID: 14960715]
3.	Anderson, J., Phan, L. and Hinnebusch, A.G. The Gcd10p/Gcd14p complex is the essential two-subunit tRNA(1-methyladenosine) methyltransferase of Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 97 (2000) 5173–5178. [DOI] [PMID: 10779558]

[EC 2.1.1.220 created 2011 (EC 2.1.1.36 created 1972, part transferred 2011 to EC 2.1.1.220)]

2.1.1.221

Accepted name:

tRNA (guanine⁹-N¹)-methyltransferase

Reaction:

S-adenosyl-L-methionine + guanine⁹ in tRNA = S-adenosyl-L-homocysteine + N¹-methylguanine⁹ in tRNA

Other name(s):

Trm10p (ambiguous); tRNA(m¹G⁹/m¹A⁹)-methyltransferase; tRNA(m¹G⁹/m¹A⁹)MTase; tRNA (guanine-N(1)-)-methyltransferase; tRNA m¹G⁹-methyltransferase; tRNA m¹G⁹ MTase

Systematic name:

S-adenosyl-L-methionine:tRNA (guanine⁹-N¹)-methyltransferase

Comments:

The enzyme from Saccharomyces cerevisiae specifically methylates guanine⁹ [1,2]. The bifunctional enzyme from Thermococcus kodakaraensis also catalyses the methylation of adenine⁹ in tRNA (cf. EC 2.1.1.218, tRNA (adenine⁹-N¹)-methyltransferase) [1].

Links to other databases:

References:

1.	Kempenaers, M., Roovers, M., Oudjama, Y., Tkaczuk, K.L., Bujnicki, J.M. and Droogmans, L. New archaeal methyltransferases forming 1-methyladenosine or 1-methyladenosine and 1-methylguanosine at position 9 of tRNA. Nucleic Acids Res. 38 (2010) 6533–6543. [DOI] [PMID: 20525789]
2.	Jackman, J.E., Montange, R.K., Malik, H.S. and Phizicky, E.M. Identification of the yeast gene encoding the tRNA m¹G methyltransferase responsible for modification at position 9. RNA 9 (2003) 574–585. [DOI] [PMID: 12702816]

[EC 2.1.1.221 created 2011 (EC 2.1.1.31 created 1971, part transferred 2011 to EC 2.1.1.221)]

2.1.1.222

Accepted name:

2-polyprenyl-6-hydroxyphenol methylase

Reaction:

S-adenosyl-L-methionine + 3-(all-trans-polyprenyl)benzene-1,2-diol = S-adenosyl-L-homocysteine + 2-methoxy-6-(all-trans-polyprenyl)phenol

For diagram of ubiquinol biosynthesis, click here

Other name(s):

ubiG (gene name, ambiguous); ubiG methyltransferase (ambiguous); 2-octaprenyl-6-hydroxyphenol methylase

Systematic name:

S-adenosyl-L-methionine:3-(all-trans-polyprenyl)benzene-1,2-diol 2-O-methyltransferase

Comments:

UbiG catalyses both methylation steps in ubiquinone biosynthesis in Escherichia coli. The second methylation is classified as EC 2.1.1.64 (3-demethylubiquinol 3-O-methyltransferase) [2]. In eukaryotes Coq3 catalyses the two methylation steps in ubiquinone biosynthesis. However, while the second methylation is common to both enzymes, the first methylation by Coq3 occurs at a different position within the pathway, and thus involves a different substrate and is classified as EC 2.1.1.114 (polyprenyldihydroxybenzoate methyltransferase). The substrate of the eukaryotic enzyme (3,4-dihydroxy-5-all-trans-polyprenylbenzoate) differs by an additional carboxylate moiety.

Links to other databases:

References:

1.	Poon, W.W., Barkovich, R.J., Hsu, A.Y., Frankel, A., Lee, P.T., Shepherd, J.N., Myles, D.C. and Clarke, C.F. Yeast and rat Coq3 and Escherichia coli UbiG polypeptides catalyze both O-methyltransferase steps in coenzyme Q biosynthesis. J. Biol. Chem. 274 (1999) 21665–21672. [DOI] [PMID: 10419476]
2.	Hsu, A.Y., Poon, W.W., Shepherd, J.A., Myles, D.C. and Clarke, C.F. Complementation of coq3 mutant yeast by mitochondrial targeting of the Escherichia coli UbiG polypeptide: evidence that UbiG catalyzes both O-methylation steps in ubiquinone biosynthesis. Biochemistry 35 (1996) 9797–9806. [DOI] [PMID: 8703953]

[EC 2.1.1.222 created 2011, modified 2013]

2.1.1.223

Accepted name:

tRNA₁^Val (adenine³⁷-N⁶)-methyltransferase

Reaction:

S-adenosyl-L-methionine + adenine³⁷ in tRNA₁^Val = S-adenosyl-L-homocysteine + N⁶-methyladenine³⁷ in tRNA₁^Val

Other name(s):

YfiC

Systematic name:

S-adenosyl-L-methionine:tRNA₁^Val (adenine³⁷-N⁶)-methyltransferase

Comments:

The enzyme specifically methylates adenine³⁷ in tRNA₁^Val (anticodon cmo5UAC).

Links to other databases:

References:

1.	Golovina, A.Y., Sergiev, P.V., Golovin, A.V., Serebryakova, M.V., Demina, I., Govorun, V.M. and Dontsova, O.A. The yfiC gene of E. coli encodes an adenine-N6 methyltransferase that specifically modifies A37 of tRNA₁^Val(cmo⁵UAC). RNA 15 (2009) 1134–1141. [DOI] [PMID: 19383770]

[EC 2.1.1.223 created 2011]

2.1.1.224

Accepted name:

23S rRNA (adenine²⁵⁰³-C⁸)-methyltransferase

Reaction:

2 S-adenosyl-L-methionine + adenine²⁵⁰³ in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5′-deoxyadenosine + 8-methyladenine²⁵⁰³ in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin

Other name(s):

Cfr (gene name)

Systematic name:

S-adenosyl-L-methionine:23S rRNA (adenine²⁵⁰³-C⁸)-methyltransferase

Comments:

This enzyme is a member of the ’AdoMet radical’ (radical SAM) family. S-Adenosyl-L-methionine acts as both a radical generator and as the source of the appended methyl group. It contains an [4Fe-4S] cluster [3,6,7]. Cfr is an plasmid-acquired methyltransferase that protects cells from the action of antibiotics [1]. The enzyme methylates adenosine at position 2503 of 23S rRNA by a radical mechanism, transferring a CH₂ group from S-adenosyl-L-methionine while retaining the hydrogen at the C-8 position of the adenine. Cfr first transfers an CH₂ group to a conserved cysteine (Cys³³⁸ in Staphylococcus aureus) [7], the generated radical from a second S-adenosyl-L-methionine then attacks the methyl group, exctracting a hydrogen. The formed radical forms a covalent intermediate with the adenine group of the tRNA [8]. The enzyme will also methylate 2-methyladenine produced by the action of EC 2.1.1.192 [23S rRNA (adenine²⁵⁰³-C²)-methyltransferase].

Links to other databases:

References:

1.	Giessing, A.M., Jensen, S.S., Rasmussen, A., Hansen, L.H., Gondela, A., Long, K., Vester, B. and Kirpekar, F. Identification of 8-methyladenosine as the modification catalyzed by the radical SAM methyltransferase Cfr that confers antibiotic resistance in bacteria. RNA 15 (2009) 327–336. [DOI] [PMID: 19144912]
2.	Kaminska, K.H., Purta, E., Hansen, L.H., Bujnicki, J.M., Vester, B. and Long, K.S. Insights into the structure, function and evolution of the radical-SAM 23S rRNA methyltransferase Cfr that confers antibiotic resistance in bacteria. Nucleic Acids Res. 38 (2010) 1652–1663. [DOI] [PMID: 20007606]
3.	Yan, F., LaMarre, J.M., Röhrich, R., Wiesner, J., Jomaa, H., Mankin, A.S. and Fujimori, D.G. RlmN and Cfr are radical SAM enzymes involved in methylation of ribosomal RNA. J. Am. Chem. Soc. 132 (2010) 3953–3964. [DOI] [PMID: 20184321]
4.	Yan, F. and Fujimori, D.G. RNA methylation by radical SAM enzymes RlmN and Cfr proceeds via methylene transfer and hydride shift. Proc. Natl. Acad. Sci. USA 108 (2011) 3930–3934. [DOI] [PMID: 21368151]
5.	Grove, T.L., Benner, J.S., Radle, M.I., Ahlum, J.H., Landgraf, B.J., Krebs, C. and Booker, S.J. A radically different mechanism for S-adenosylmethionine-dependent methyltransferases. Science 332 (2011) 604–607. [DOI] [PMID: 21415317]
6.	Boal, A.K., Grove, T.L., McLaughlin, M.I., Yennawar, N.H., Booker, S.J. and Rosenzweig, A.C. Structural basis for methyl transfer by a radical SAM enzyme. Science 332 (2011) 1089–1092. [DOI] [PMID: 21527678]
7.	Grove, T.L., Radle, M.I., Krebs, C. and Booker, S.J. Cfr and RlmN contain a single [4Fe-4S] cluster, which directs two distinct reactivities for S-adenosylmethionine: methyl transfer by S_N2 displacement and radical generation. J. Am. Chem. Soc. 133 (2011) 19586–19589. [DOI] [PMID: 21916495]
8.	Grove, T.L., Livada, J., Schwalm, E.L., Green, M.T., Booker, S.J. and Silakov, A. A substrate radical intermediate in catalysis by the antibiotic resistance protein Cfr. Nat. Chem. Biol. 9 (2013) 422–427. [DOI] [PMID: 23644479]

[EC 2.1.1.224 created 2011, modified 2014]

2.1.1.225

Accepted name:

tRNA:m⁴X modification enzyme

Reaction:

(1) S-adenosyl-L-methionine + cytidine⁴ in tRNA^Pro = S-adenosyl-L-homocysteine + 2′-O-methylcytidine⁴ in tRNA^Pro
(2) S-adenosyl-L-methionine + cytidine⁴ in tRNA^Gly(GCC) = S-adenosyl-L-homocysteine + 2′-O-methylcytidine⁴ in tRNA^Gly(GCC)
(3) S-adenosyl-L-methionine + adenosine⁴ in tRNA^His = S-adenosyl-L-homocysteine + 2′-O-methyladenosine⁴ in tRNA^His

For diagram of bornane and related monoterpenoids, click here

Other name(s):

TRM13; Trm13p; tRNA:Xm4 modification enzyme

Systematic name:

S-adenosyl-L-methionine:tRNA^Pro/His/Gly(GCC) (cytidine/adenosine⁴-2′-O)-methyltransferase

Comments:

The enzyme from Saccharomyces cerevisiae 2′-O-methylates cytidine⁴ in tRNA^Pro and tRNA^Gly(GCC), and adenosine⁴ in tRNA^His.

Links to other databases:

References:

1.	Wilkinson, M.L., Crary, S.M., Jackman, J.E., Grayhack, E.J. and Phizicky, E.M. The 2′-O-methyltransferase responsible for modification of yeast tRNA at position 4. RNA 13 (2007) 404–413. [DOI] [PMID: 17242307]

[EC 2.1.1.225 created 2011]

2.1.1.226

Accepted name:

23S rRNA (cytidine¹⁹²⁰-2′-O)-methyltransferase

Reaction:

S-adenosyl-L-methionine + cytidine¹⁹²⁰ in 23S rRNA = S-adenosyl-L-homocysteine + 2′-O-methylcytidine¹⁹²⁰ in 23S rRNA

Other name(s):

TlyA (ambiguous)

Systematic name:

S-adenosyl-L-methionine:23S rRNA (cytidine¹⁹²⁰-2′-O)-methyltransferase

Comments:

The bifunctional enzyme from Mycobacterium tuberculosis 2′-O-methylates cytidine¹⁹²⁰ in helix 69 of 23S rRNA and cytidine¹⁴⁰⁹ in helix 44 of 16S rRNA (cf. EC 2.1.1.227, 16S rRNA (cytidine¹⁴⁰⁹-2′-O)-methyltransferase). These methylations result in increased susceptibility to the antibiotics capreomycin and viomycin.

Links to other databases:

References:

1.	Johansen, S.K., Maus, C.E., Plikaytis, B.B. and Douthwaite, S. Capreomycin binds across the ribosomal subunit interface using tlyA-encoded 2′-O-methylations in 16S and 23S rRNAs. Mol. Cell 23 (2006) 173–182. [DOI] [PMID: 16857584]
2.	Maus, C.E., Plikaytis, B.B. and Shinnick, T.M. Mutation of tlyA confers capreomycin resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 49 (2005) 571–577. [DOI] [PMID: 15673735]

[EC 2.1.1.226 created 2011]

2.1.1.227

Accepted name:

16S rRNA (cytidine¹⁴⁰⁹-2′-O)-methyltransferase

Reaction:

S-adenosyl-L-methionine + cytidine¹⁴⁰⁹ in 16S rRNA = S-adenosyl-L-homocysteine + 2′-O-methylcytidine¹⁴⁰⁹ in 16S rRNA

Other name(s):

TlyA (ambiguous)

Systematic name:

S-adenosyl-L-methionine:16S rRNA (cytidine¹⁴⁰⁹-2′-O)-methyltransferase

Comments:

The bifunctional enzyme from Mycobacterium tuberculosis 2′-O-methylates cytidine¹⁴⁰⁹ in helix 44 of 16S rRNA and cytidine¹⁹²⁰ in helix 69 of 23S rRNA (cf. EC 2.1.1.226, 23S rRNA (cytidine¹⁹²⁰-2′-O)-methyltransferase).

Links to other databases:

References:

1.	Johansen, S.K., Maus, C.E., Plikaytis, B.B. and Douthwaite, S. Capreomycin binds across the ribosomal subunit interface using tlyA-encoded 2′-O-methylations in 16S and 23S rRNAs. Mol. Cell 23 (2006) 173–182. [DOI] [PMID: 16857584]
2.	Maus, C.E., Plikaytis, B.B. and Shinnick, T.M. Mutation of tlyA confers capreomycin resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 49 (2005) 571–577. [DOI] [PMID: 15673735]

[EC 2.1.1.227 created 2011]

2.1.1.228

Accepted name:

tRNA (guanine³⁷-N¹)-methyltransferase

Reaction:

S-adenosyl-L-methionine + guanine³⁷ in tRNA = S-adenosyl-L-homocysteine + N¹-methylguanine³⁷ in tRNA

For diagram of wyosine biosynthesis, click here

Other name(s):

TrmD; tRNA (m¹G³⁷) methyltransferase; transfer RNA (m¹G³⁷) methyltransferase; Trm5p; TRMT5; tRNA-(N¹G37) methyltransferase; MJ0883 (gene name)

Systematic name:

S-adenosyl-L-methionine:tRNA (guanine³⁷-N¹)-methyltransferase

Comments:

This enzyme is important for the maintenance of the correct reading frame during translation. Unlike TrmD from Escherichia coli, which recognizes the G36pG37 motif preferentially, the human enzyme (encoded by TRMT5) also methylates inosine at position 37 [4].

Links to other databases:

References:

1.	Takeda, H., Toyooka, T., Ikeuchi, Y., Yokobori, S., Okadome, K., Takano, F., Oshima, T., Suzuki, T., Endo, Y. and Hori, H. The substrate specificity of tRNA (m¹G³⁷) methyltransferase (TrmD) from Aquifex aeolicus. Genes Cells 11 (2006) 1353–1365. [DOI] [PMID: 17121543]
2.	Lee, C., Kramer, G., Graham, D.E. and Appling, D.R. Yeast mitochondrial initiator tRNA is methylated at guanosine 37 by the Trm5-encoded tRNA (guanine-N¹-)-methyltransferase. J. Biol. Chem. 282 (2007) 27744–27753. [DOI] [PMID: 17652090]
3.	O'Dwyer, K., Watts, J.M., Biswas, S., Ambrad, J., Barber, M., Brule, H., Petit, C., Holmes, D.J., Zalacain, M. and Holmes, W.M. Characterization of Streptococcus pneumoniae TrmD, a tRNA methyltransferase essential for growth. J. Bacteriol. 186 (2004) 2346–2354. [DOI] [PMID: 15060037]
4.	Brule, H., Elliott, M., Redlak, M., Zehner, Z.E. and Holmes, W.M. Isolation and characterization of the human tRNA-(N1G37) methyltransferase (TRM5) and comparison to the Escherichia coli TrmD protein. Biochemistry 43 (2004) 9243–9255. [DOI] [PMID: 15248782]
5.	Goto-Ito, S., Ito, T., Ishii, R., Muto, Y., Bessho, Y. and Yokoyama, S. Crystal structure of archaeal RNA(m¹G37)methyltransferase aTrm5. Proteins 72 (2008) 1274–1289. [DOI] [PMID: 18384044]
6.	Ahn, H.J., Kim, H.W., Yoon, H.J., Lee, B.I., Suh, S.W. and Yang, J.K. Crystal structure of tRNA(m¹G³⁷)methyltransferase: insights into tRNA recognition. EMBO J. 22 (2003) 2593–2603. [DOI] [PMID: 12773376]

[EC 2.1.1.228 created 2011 (EC 2.1.1.31 created 1971, part transferred 2011 to EC 2.1.1.228)]

2.1.1.229

Accepted name:

tRNA (carboxymethyluridine³⁴-5-O)-methyltransferase

Reaction:

S-adenosyl-L-methionine + carboxymethyluridine³⁴ in tRNA = S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine³⁴ in tRNA

Glossary:

5-methoxycarboxymethyluridine = 5-(2-methoxy-2-oxoethyl)uridine

Other name(s):

ALKBH8; ABH8; Trm9; tRNA methyltransferase 9

Systematic name:

S-adenosyl-L-methionine:tRNA (carboxymethyluridine³⁴-5-O)-methyltransferase

Comments:

The enzyme catalyses the posttranslational modification of uridine residues at the wobble position 34 of the anticodon loop of tRNA.

Links to other databases:

References:

1.	Fu, D., Brophy, J.A., Chan, C.T., Atmore, K.A., Begley, U., Paules, R.S., Dedon, P.C., Begley, T.J. and Samson, L.D. Human AlkB homolog ABH8 Is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival. Mol. Cell Biol. 30 (2010) 2449–2459. [DOI] [PMID: 20308323]
2.	Songe-Møller, L., van den Born, E., Leihne, V., Vågbø, C.B., Kristoffersen, T., Krokan, H.E., Kirpekar, F., Falnes, P.Ø. and Klungland, A. Mammalian ALKBH8 possesses tRNA methyltransferase activity required for the biogenesis of multiple wobble uridine modifications implicated in translational decoding. Mol. Cell Biol. 30 (2010) 1814–1827. [DOI] [PMID: 20123966]
3.	Kalhor, H.R. and Clarke, S. Novel methyltransferase for modified uridine residues at the wobble position of tRNA. Mol. Cell Biol. 23 (2003) 9283–9292. [DOI] [PMID: 14645538]

[EC 2.1.1.229 created 2011]

2.1.1.230

Accepted name:

23S rRNA (adenosine¹⁰⁶⁷-2′-O)-methyltransferase

Reaction:

S-adenosyl-L-methionine + adenosine¹⁰⁶⁷ in 23S rRNA = S-adenosyl-L-homocysteine + 2′-O-methyladenosine¹⁰⁶⁷ in 23S rRNA

Other name(s):

23S rRNA A¹⁰⁶⁷ 2′-methyltransferase; thiostrepton-resistance methylase; nosiheptide-resistance methyltransferase

Systematic name:

S-adenosyl-L-methionine:23S rRNA (adenosine¹⁰⁶⁷-2′-O)-methyltransferase

Comments:

The methylase that is responsible for autoimmunity in the thiostrepton producer Streptomyces azureus, renders ribosomes completely resistant to thiostrepton [2].

Links to other databases:

References:

1.	Bechthold, A. and Floss, H.G. Overexpression of the thiostrepton-resistance gene from Streptomyces azureus in Escherichia coli and characterization of recognition sites of the 23S rRNA A¹⁰⁶⁷ 2′-methyltransferase in the guanosine triphosphatase center of 23S ribosomal RNA. Eur. J. Biochem. 224 (1994) 431–437. [DOI] [PMID: 7925357]
2.	Thompson, J., Schmidt, F. and Cundliffe, E. Site of action of a ribosomal RNA methylase conferring resistance to thiostrepton. J. Biol. Chem. 257 (1982) 7915–7917. [PMID: 6806287]
3.	Thompson, J. and Cundliffe, E. Purification and properties of an RNA methylase produced by Streptomyces azureus and involved in resistance to thiostrepton. J. Gen. Microbiol. 124 (1981) 291–297.
4.	Yang, H., Wang, Z., Shen, Y., Wang, P., Jia, X., Zhao, L., Zhou, P., Gong, R., Li, Z., Yang, Y., Chen, D., Murchie, A.I. and Xu, Y. Crystal structure of the nosiheptide-resistance methyltransferase of Streptomyces actuosus. Biochemistry 49 (2010) 6440–6450. [DOI] [PMID: 20550164]

[EC 2.1.1.230 created 2011]

2.1.1.231

Accepted name:

flavonoid 4′-O-methyltransferase

Reaction:

S-adenosyl-L-methionine + a 4′-hydroxyflavanone = S-adenosyl-L-homocysteine + a 4′-methoxyflavanone

For diagram of naringenin methyl ethers biosynthesis, click here

Glossary:

naringenin = 4′,5,7-trihydroxyflavan-4-one

Other name(s):

SOMT-2; 4′-hydroxyisoflavone methyltransferase

Systematic name:

S-adenosyl-L-methionine:flavonoid 4′-O-methyltransferase

Comments:

The enzyme catalyses the 4′-methylation of naringenin. In vitro it catalyses the 4′-methylation of apigenin, quercetin, daidzein and genistein.

Links to other databases:

References:

1.	Kim, D.H., Kim, B.G., Lee, Y., Ryu, J.Y., Lim, Y., Hur, H.G. and Ahn, J.H. Regiospecific methylation of naringenin to ponciretin by soybean O-methyltransferase expressed in Escherichia coli. J. Biotechnol. 119 (2005) 155–162. [DOI] [PMID: 15961179]

[EC 2.1.1.231 created 2011]

2.1.1.232

Accepted name:

naringenin 7-O-methyltransferase

Reaction:

S-adenosyl-L-methionine + (2S)-naringenin = S-adenosyl-L-homocysteine + (2S)-sakuranetin

For diagram of naringenin methyl ethers biosynthesis, click here

Glossary:

(2S)-naringenin = (2S)-5,7,4′-trihydroxyflavan-4-one
(2S)-sakuranetin = (2S)-5,4′-dihydroxy-7-methoxyflavan-4-one

Other name(s):

NOMT

Systematic name:

S-adenosyl-L-methionine:(2S)-5,7,4′-trihydroxyflavanone 7-O-methyltransferase

Comments:

The enzyme is involved in the biosynthesis of the sakuranetin, an inducible defense mechanism of the plant Oryza sativa (Asian rice) against pathogen attack.

Links to other databases:

References:

1.	Rakwal, R., Agrawal, G.K., Yonekura, M. and Kodama, O. Naringenin 7-O-methyltransferase involved in the biosynthesis of the flavanone phytoalexin sakuranetin from rice (Oryza sativa L.). Plant Sci. 155 (2000) 213–221. [DOI] [PMID: 10814825]

[EC 2.1.1.232 created 2011]

2.1.1.233

Accepted name:

[phosphatase 2A protein]-leucine-carboxy methyltransferase

Reaction:

S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine = S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester

Other name(s):

leucine carboxy methyltransferase-1; LCMT1

Systematic name:

S-adenosyl-L-methionine:[phosphatase 2A protein]-leucine O-methyltransferase

Comments:

Methylates the C-terminal leucine of phosphatase 2A. A key regulator of protein phosphatase 2A. The methyl ester is hydrolysed by EC 3.1.1.89 (protein phosphatase methylesterase-1). Occurs mainly in the cytoplasm, Golgi region and late endosomes.

Links to other databases:

References:

1.	De Baere, I., Derua, R., Janssens, V., Van Hoof, C., Waelkens, E., Merlevede, W. and Goris, J. Purification of porcine brain protein phosphatase 2A leucine carboxyl methyltransferase and cloning of the human homologue. Biochemistry 38 (1999) 16539–16547. [DOI] [PMID: 10600115]
2.	Tsai, M.L., Cronin, N. and Djordjevic, S. The structure of human leucine carboxyl methyltransferase 1 that regulates protein phosphatase PP2A. Acta Crystallogr. D Biol. Crystallogr. 67 (2011) 14–24. [DOI] [PMID: 21206058]

[EC 2.1.1.233 created 2011]

2.1.1.234

Accepted name:

dTDP-3-amino-3,4,6-trideoxy-α-D-glucopyranose N,N-dimethyltransferase

Reaction:

2 S-adenosyl-L-methionine + dTDP-3-amino-3,4,6-trideoxy-α-D-glucopyranose = 2 S-adenosyl-L-homocysteine + dTDP-3-dimethylamino-3,4,6-trideoxy-α-D-glucopyranose

For diagram of dTDP-D-desosamine biosynthesis, click here

Glossary:

α-D-desosamine = 3-dimethylamino-3,4,6-trideoxy-α-D-glucopyranose
dTDP-3-dimethylamino-3,4,6-trideoxy-α-D-glucopyranose = dTDP-D-desosamine

Other name(s):

DesVI

Systematic name:

S-adenosyl-L-methionine:dTDP-3-amino-3,4,6-trideoxy-α-D-glucopyranose 3-N,N-dimethyltransferase

Comments:

The enzyme is involved in the biosynthesis of desosamine, a 3-(dimethylamino)-3,4,6-trideoxyhexose found in certain macrolide antibiotics such as erthyromycin, azithromycin, and clarithromycin.

Links to other databases:

References:

1.	Chen, H., Yamase, H., Murakami, K., Chang, C.W., Zhao, L., Zhao, Z. and Liu, H.W. Expression, purification, and characterization of two N,N-dimethyltransferases, tylM1 and desVI, involved in the biosynthesis of mycaminose and desosamine. Biochemistry 41 (2002) 9165–9183. [DOI] [PMID: 12119032]
2.	Burgie, E.S. and Holden, H.M. Three-dimensional structure of DesVI from Streptomyces venezuelae: a sugar N,N-dimethyltransferase required for dTDP-desosamine biosynthesis. Biochemistry 47 (2008) 3982–3988. [DOI] [PMID: 18327916]

[EC 2.1.1.234 created 2011]

2.1.1.235

Accepted name:

dTDP-3-amino-3,6-dideoxy-α-D-glucopyranose N,N-dimethyltransferase

Reaction:

2 S-adenosyl-L-methionine + dTDP-3-amino-3,6-dideoxy-α-D-glucopyranose = 2 S-adenosyl-L-homocysteine + dTDP-3-dimethylamino-3,6-dideoxy-α-D-glucopyranose

For diagram of dTDP-D-mycaminose biosynthesis, click here

Glossary:

dTDP-D-mycaminose = dTDP-3-dimethylamino-3,6-dideoxy-α-D-glucopyranose

Other name(s):

TylM1

Systematic name:

S-adenosyl-L-methionine:dTDP-3-amino-3,6-dideoxy-α-D-glucopyranose 3-N,N-dimethyltransferase

Comments:

The enzyme is involved in the biosynthesis of mycaminose, an essential structural component of the macrolide antibiotic tylosin, which is produced by the bacterium Streptomyces fradiae.

Links to other databases:

References:

1.	Chen, H., Yamase, H., Murakami, K., Chang, C.W., Zhao, L., Zhao, Z. and Liu, H.W. Expression, purification, and characterization of two N,N-dimethyltransferases, tylM1 and desVI, involved in the biosynthesis of mycaminose and desosamine. Biochemistry 41 (2002) 9165–9183. [DOI] [PMID: 12119032]
2.	Carney, A.E. and Holden, H.M. Molecular architecture of TylM1 from Streptomyces fradiae: an N,N-dimethyltransferase involved in the production of dTDP-D-mycaminose. Biochemistry 50 (2011) 780–787. [DOI] [PMID: 21142177]

[EC 2.1.1.235 created 2011]

2.1.1.236

Accepted name:

dTDP-3-amino-3,6-dideoxy-α-D-galactopyranose N,N-dimethyltransferase

Reaction:

2 S-adenosyl-L-methionine + dTDP-3-amino-3,6-dideoxy-α-D-galactopyranose = 2 S-adenosyl-L-homocysteine + dTDP-3-dimethylamino-3,6-dideoxy-α-D-galactopyranose

For diagram of dTDP-Fuc3NAc, dTDP-Fuc4NAc and dTDP-Fuc3NMe₂ biosynthesis, click here

Glossary:

dTDP-3-dimethylamino-3,6-dideoxy-α-D-galactopyranose = dTDP-D-ravidosamine

Other name(s):

RavNMT

Systematic name:

S-adenosyl-L-methionine:dTDP-3-amino-3,6-dideoxy-α-D-galactopyranose 3-N,N-dimethyltransferase

Comments:

The enzyme is involved in the synthesis of dTDP-D-ravidosamine, the amino sugar moiety of the antibiotic ravidomycin V, which is produced by the bacterium Streptomyces ravidus.

Links to other databases:

References:

1.	Kharel, M.K., Lian, H. and Rohr, J. Characterization of the TDP-D-ravidosamine biosynthetic pathway: one-pot enzymatic synthesis of TDP-D-ravidosamine from thymidine-5-phosphate and glucose-1-phosphate. Org. Biomol. Chem. 9 (2011) 1799–1808. [DOI] [PMID: 21264378]

[EC 2.1.1.236 created 2011]

2.1.1.237

Accepted name:

mycinamicin III 3′′-O-methyltransferase

Reaction:

S-adenosyl-L-methionine + mycinamicin III = S-adenosyl-L-homocysteine + mycinamicin IV

For diagram of mycinamycin biosynthesis, click here

Glossary:

mycinamicin III = [(2R,3R,4E,6E,9R,11S,12S,13S,14E)-2-ethyl-9,11,13-trimethyl-8,16-dioxo-12-{[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy}oxacyclohexadeca-4,6,14-trien-3-yl]methyl 6-deoxy-2-O-methyl-β-D-allopyranoside
mycinamicin IV = [(2R,3R,4E,6E,9R,11S,12S,13S,14E)-2-ethyl-9,11,13-trimethyl-8,16-dioxo-12-{[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy}oxacyclohexadeca-4,6,14-trien-3-yl]methyl 6-deoxy-2,3-di-O-methyl-β-D-allopyranoside

Other name(s):

MycF

Systematic name:

S-adenosyl-L-methionine:mycinamicin III 3′′-O-methyltransferase

Comments:

The enzyme is involved in the biosynthesis of mycinamicin macrolide antibiotics.

Links to other databases:

References:

1.	Li, S., Anzai, Y., Kinoshita, K., Kato, F. and Sherman, D.H. Functional analysis of MycE and MycF, two O-methyltransferases involved in the biosynthesis of mycinamicin macrolide antibiotics. ChemBioChem 10 (2009) 1297–1301. [DOI] [PMID: 19415708]

[EC 2.1.1.237 created 2011]

2.1.1.238

Accepted name:

mycinamicin VI 2′′-O-methyltransferase

Reaction:

S-adenosyl-L-methionine + mycinamicin VI = S-adenosyl-L-homocysteine + mycinamicin III

For diagram of mycinamycin biosynthesis, click here

Glossary:

mycinamicin III = [(2R,3R,4E,6E,9R,11S,12S,13S,14E)-2-ethyl-9,11,13-trimethyl-8,16-dioxo-12-{[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy}oxacyclohexadeca-4,6,14-trien-3-yl]methyl 6-deoxy-2-O-methyl-β-D-allopyranoside
mycinamicin VI = [(2R,3R,4E,6E,9R,11S,12S,13S,14E)-2-ethyl-9,11,13-trimethyl-8,16-dioxo-12-{[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy}oxacyclohexadeca-4,6,14-trien-3-yl]methyl 6-deoxy-β-D-allopyranoside

Other name(s):

MycE

Systematic name:

S-adenosyl-L-methionine:mycinamicin VI 2′′-O-methyltransferase

Comments:

The enzyme is involved in the biosynthesis of mycinamicin macrolide antibiotics. Requires Mg²⁺ for optimal activity.

Links to other databases:

References:

1.	Li, S., Anzai, Y., Kinoshita, K., Kato, F. and Sherman, D.H. Functional analysis of MycE and MycF, two O-methyltransferases involved in the biosynthesis of mycinamicin macrolide antibiotics. ChemBioChem 10 (2009) 1297–1301. [DOI] [PMID: 19415708]

[EC 2.1.1.238 created 2011]

*EC

2.3.1.135

Accepted name:

phosphatidylcholine—retinol O-acyltransferase

Reaction:

phosphatidylcholine + retinol—[cellular-retinol-binding-protein] = 2-acylglycerophosphocholine + retinyl-ester—[cellular-retinol-binding-protein]

Glossary:

phosphatidylcholine = lecithin

Other name(s):

lecithin—retinol acyltransferase; phosphatidylcholine:retinol-(cellular-retinol-binding-protein) O-acyltransferase; lecithin:retinol acyltransferase; lecithin-retinol acyltransferase; retinyl ester synthase; LRAT; lecithin retinol acyl transferase

Systematic name:

phosphatidylcholine:retinol—[cellular-retinol-binding-protein] O-acyltransferase

Comments:

A key enzyme in retinoid metabolism, catalysing the transfer of an acyl group from the sn-1 position of phosphatidylcholine to retinol, forming retinyl esters which are then stored. Recognizes the substrate both in free form and when bound to cellular-retinol-binding-protein, but has higher affinity for the bound form. Can also esterify 11-cis-retinol.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 117444-03-8

References:

1.	MacDonald, P.N. and Ong, D.E. Evidence for a lecithin-retinol acyltransferase activity in the rat small intestine. J. Biol. Chem. 263 (1988) 12478–12482. [PMID: 3410848]
2.	Saari, J.C. and Bredberg, D.L. Lecithin:retinol acyltransferase in retinal pigment epithelial microsomes. J. Biol. Chem. 264 (1989) 8636. [PMID: 2722792]
3.	Saari, J.C., Bredberg, D.L. and Farrell, D.F. Retinol esterification in bovine retinal pigment epithelium: reversibility of lecithin:retinol acyltransferase. Biochem. J. 291 (1993) 697–700. [PMID: 8489497]
4.	Mata, N.L. and Tsin, A.T. Distribution of 11-cis LRAT, 11-cis RD and 11-cis REH in bovine retinal pigment epithelium membranes. Biochim. Biophys. Acta 1394 (1998) 16–22. [DOI] [PMID: 9767084]
5.	Ruiz, A., Winston, A., Lim, Y.H., Gilbert, B.A., Rando, R.R. and Bok, D. Molecular and biochemical characterization of lecithin retinol acyltransferase. J. Biol. Chem. 274 (1999) 3834–3841. [DOI] [PMID: 9920938]

[EC 2.3.1.135 created 1992, modified 2011]

*EC

2.3.2.2

Accepted name:

γ-glutamyltransferase

Reaction:

a (5-L-glutamyl)-peptide + an amino acid = a peptide + a 5-L-glutamyl amino acid

Other name(s):

glutamyl transpeptidase; α-glutamyl transpeptidase; γ-glutamyl peptidyltransferase; γ-glutamyl transpeptidase (ambiguous); γ-GPT; γ-GT; γ-GTP; L-γ-glutamyl transpeptidase; L-γ-glutamyltransferase; L-glutamyltransferase; GGT (ambiguous); γ-glutamyltranspeptidase (ambiguous)

Systematic name:

(5-L-glutamyl)-peptide:amino-acid 5-glutamyltransferase

Comments:

The mammlian enzyme is part of the cell antioxidant defense mechanism. It initiates extracellular glutathione (GSH) breakdown, provides cells with a local cysteine supply and contributes to maintain intracelular GSH levels. The protein also has EC 3.4.19.13 (glutathione hydrolase) activity [3-4]. The enzyme consists of two chains that are created by the proteolytic cleavage of a single precursor polypeptide. The N-terminal L-threonine of the C-terminal subunit functions as the active site for both the cleavage and the hydrolysis reactions [3-4].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9046-27-9

References:

1.	Goore, M.Y. and Thompson, J.F. γ-Glutamyl transpeptidase from kidney bean fruit. I. Purification and mechanism of action. Biochim. Biophys. Acta 132 (1967) 15–26. [DOI] [PMID: 6030345]
2.	Leibach, F.H. and Binkley, F. γ-Glutamyl transferase of swine kidney. Arch. Biochem. Biophys. 127 (1968) 292–301. [PMID: 5698023]
3.	Okada, T., Suzuki, H., Wada, K., Kumagai, H. and Fukuyama, K. Crystal structures of γ-glutamyltranspeptidase from Escherichia coli, a key enzyme in glutathione metabolism, and its reaction intermediate. Proc. Natl. Acad. Sci. USA 103 (2006) 6471–6476. [DOI] [PMID: 16618936]
4.	Boanca, G., Sand, A., Okada, T., Suzuki, H., Kumagai, H., Fukuyama, K. and Barycki, J.J. Autoprocessing of Helicobacter pylori γ-glutamyltranspeptidase leads to the formation of a threonine-threonine catalytic dyad. J. Biol. Chem. 282 (2007) 534–541. [DOI] [PMID: 17107958]
5.	Wickham, S., West, M.B., Cook, P.F. and Hanigan, M.H. Gamma-glutamyl compounds: substrate specificity of γ-glutamyl transpeptidase enzymes. Anal. Biochem. 414 (2011) 208–214. [DOI] [PMID: 21447318]

[EC 2.3.2.2 created 1972, modified 1976, modified 2011]

*EC

2.4.1.180

Accepted name:

lipopolysaccharide N-acetylmannosaminouronosyltransferase

Reaction:

UDP-N-acetyl-α-D-mannosaminouronate + N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol = UDP + N-acetyl-β-D-mannosaminouronyl-(1→4)-N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol

Glossary:

N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol = lipid I = GlcNAc-pyrophosphorylundecaprenol = ditrans,octacis-undecaprenyl-N-acetyl-α-D-glucosaminyl diphosphate

Other name(s):

ManNAcA transferase; uridine diphosphoacetylmannosaminuronate-acetylglucosaminylpyrophosphorylundecaprenol acetylmannosaminuronosyltransferase; UDP-N-acetyl-β-D-mannosaminouronate:lipid I N-acetyl-β-D-mannosaminouronosyltransferase (incorrect)

Systematic name:

UDP-N-acetyl-α-D-mannosaminouronate:lipid I N-acetyl-α-D-mannosaminouronosyltransferase

Comments:

Involved in the biosynthesis of common antigen in Enterobacteriaceae.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 113478-30-1

References:

Barr, K., Ward, S., Meier-Dieter, U., Mayer, H. and Rick, P.D. Characterization of an Escherichia coli rff mutant defective in transfer of N-acetylmannosaminuronic acid (ManNAcA) from UDP-ManNAcA to a lipid-linked intermediate involved in enterobacterial common antigen synthesis. J. Bacteriol. 170 (1988) 228–233. [DOI] [PMID: 3275612]

[EC 2.4.1.180 created 1990, modified 2011]

2.4.1.271

Accepted name:

crocetin glucosyltransferase

Reaction:

(1) UDP-α-D-glucose + crocetin = UDP + β-D-glucosyl crocetin
(2) UDP-α-D-glucose + β-D-glucosyl crocetin = UDP + bis(β-D-glucosyl) crocetin
(3) UDP-α-D-glucose + β-D-gentiobiosyl crocetin = UDP + β-D-gentiobiosyl β-D-glucosyl crocetin

For diagram of crocin biosynthesis, click here

Other name(s):

crocetin GTase; UGTCs2; UGT75L6; UDP-glucose:crocetin glucosyltransferase; UDP-glucose:crocetin 8-O-D-glucosyltransferase

Systematic name:

UDP-α-D-glucose:crocetin 8-O-D-glucosyltransferase

Comments:

In the plants Crocus sativus and Gardenia jasminoides this enzyme esterifies a free carboxyl group of crocetin and some crocetin glycosyl esters. The enzyme from Gardenia can also form glucosyl esters with 4-coumarate, caffeate and ferulate [3].

Links to other databases:

References:

1.	Côté, F., Cormier, F., Dufresne, C. and Willemot, C. Properties of a glucosyltransferase involved in crocin synthesis. Plant Sci. 153 (2000) 55–63.
2.	Moraga, A.R., Nohales, P.F., Perez, J.A. and Gomez-Gomez, L. Glucosylation of the saffron apocarotenoid crocetin by a glucosyltransferase isolated from Crocus sativus stigmas. Planta 219 (2004) 955–966. [DOI] [PMID: 15605174]
3.	Nagatoshi, M., Terasaka, K., Owaki, M., Sota, M., Inukai, T., Nagatsu, A. and Mizukami, H. UGT75L6 and UGT94E5 mediate sequential glucosylation of crocetin to crocin in Gardenia jasminoides. FEBS Lett. 586 (2012) 1055–1061. [DOI] [PMID: 22569263]

[EC 2.4.1.271 created 2011]

2.4.1.272

Accepted name:

soyasapogenol B glucuronide galactosyltransferase

Reaction:

UDP-α-D-galactose + soyasapogenol B 3-O-β-D-glucuronide = UDP + soyasaponin III

For diagram of soyasapogenol biosynthesis, click here

Glossary:

soyasaponin III = 3β-(2-O-β-D-galactopyranosyl-β-D-glucopyranosyloxyuronic acid)olean-12-ene-22β,24-diol

Other name(s):

UDP-galactose:SBMG-galactosyltransferase; UGT73P2; GmSGT2 (gene name); UDP-galactose:soyasapogenol B 3-O-glucuronide β-D-galactosyltransferase

Systematic name:

UDP-α-D-galactose:soyasapogenol B 3-O-glucuronide β-D-galactosyltransferase

Comments:

Part of the biosynthetic pathway for soyasaponins.

Links to other databases:

References:

1.	Shibuya, M., Nishimura, K., Yasuyama, N. and Ebizuka, Y. Identification and characterization of glycosyltransferases involved in the biosynthesis of soyasaponin I in Glycine max. FEBS Lett. 584 (2010) 2258–2264. [DOI] [PMID: 20350545]

[EC 2.4.1.272 created 2011]

2.4.1.273

Accepted name:

soyasaponin III rhamnosyltransferase

Reaction:

UDP-β-L-rhamnose + soyasaponin III = UDP + soyasaponin I

For diagram of soyasapogenol biosynthesis, click here

Glossary:

UDP-β-L-rhamnose = UDP-6-deoxy-β-L-mannose

Other name(s):

UGT91H4; GmSGT3 (gene name); UDP-rhamnose:soyasaponin III rhamnosyltransferase

Systematic name:

UDP-β-L-rhamnose:soyasaponin III rhamnosyltransferase

Comments:

Part of the biosynthetic pathway for soyasaponins.

Links to other databases:

References:

1.	Shibuya, M., Nishimura, K., Yasuyama, N. and Ebizuka, Y. Identification and characterization of glycosyltransferases involved in the biosynthesis of soyasaponin I in Glycine max. FEBS Lett. 584 (2010) 2258–2264. [DOI] [PMID: 20350545]

[EC 2.4.1.273 created 2011]

2.4.1.274

Accepted name:

glucosylceramide β-1,4-galactosyltransferase

Reaction:

UDP-α-D-galactose + β-D-glucosyl-(1↔1)-ceramide = UDP + β-D-galactosyl-(1→4)-β-D-glucosyl-(1↔1)-ceramide

For diagram of glycolipid biosynthesis, click here

Other name(s):

lactosylceramide synthase; uridine diphosphate-galactose:glucosyl ceramide β 1-4 galactosyltransferase; UDP-Gal:glucosylceramide β1→4galactosyltransferase; GalT-2 (misleading); UDP-galactose:β-D-glucosyl-(1↔1)-ceramide β-1,4-galactosyltransferase

Systematic name:

UDP-α-D-galactose:β-D-glucosyl-(1↔1)-ceramide 4-β-D-galactosyltransferase

Comments:

Involved in the synthesis of several different major classes of glycosphingolipids.

Links to other databases:

References:

1.	Chatterjee, S. and Castiglione, E. UDPgalactose:glucosylceramide β1→4-galactosyltransferase activity in human proximal tubular cells from normal and familial hypercholesterolemic homozygotes. Biochim. Biophys. Acta 923 (1987) 136–142. [DOI] [PMID: 3099851]
2.	Trinchera, M., Fiorilli, A. and Ghidoni, R. Localization in the Golgi apparatus of rat liver UDP-Gal:glucosylceramide β1→4galactosyltransferase. Biochemistry 30 (1991) 2719–2724. [PMID: 1900430]
3.	Chatterjee, S., Ghosh, N. and Khurana, S. Purification of uridine diphosphate-galactose:glucosyl ceramide, β 1-4 galactosyltransferase from human kidney. J. Biol. Chem. 267 (1992) 7148–7153. [PMID: 1551920]
4.	Nomura, T., Takizawa, M., Aoki, J., Arai, H., Inoue, K., Wakisaka, E., Yoshizuka, N., Imokawa, G., Dohmae, N., Takio, K., Hattori, M. and Matsuo, N. Purification, cDNA cloning, and expression of UDP-Gal: glucosylceramide β-1,4-galactosyltransferase from rat brain. J. Biol. Chem. 273 (1998) 13570–13577. [DOI] [PMID: 9593693]
5.	Takizawa, M., Nomura, T., Wakisaka, E., Yoshizuka, N., Aoki, J., Arai, H., Inoue, K., Hattori, M. and Matsuo, N. cDNA cloning and expression of human lactosylceramide synthase. Biochim. Biophys. Acta 1438 (1999) 301–304. [DOI] [PMID: 10320813]

[EC 2.4.1.274 created 2011]

2.4.1.275

Accepted name:

neolactotriaosylceramide β-1,4-galactosyltransferase

Reaction:

UDP-α-D-galactose + N-acetyl-β-D-glucosaminyl-(1→3)-β-D-galactosyl-(1→4)-β-D-glucosyl-(1↔1)-ceramide = UDP + β-D-galactosyl-(1→4)-N-acetyl-β-D-glucosaminyl-(1→3)-β-D-galactosyl-(1→4)-β-D-glucosyl-(1↔1)-ceramide

For diagram of neolactotetraosylceramide biosynthesis, click here

Glossary:

N-acetyl-β-D-glucosaminyl-(1→3)-β-D-galactosyl-(1→4)-β-D-glucosyl-(1↔1)-ceramide = neolactotriaosylceramide

Other name(s):

β4Gal-T4; UDP-galactose:N-acetyl-β-D-glucosaminyl-(1→3)-β-D-galactosyl-(1→4)-β-D-glucosyl-(1↔1)-ceramide β-1,4-galactosyltransferase; lactotriaosylceramide β-1,4-galactosyltransferase (incorrect)

Systematic name:

UDP-α-D-galactose:N-acetyl-β-D-glucosaminyl-(1→3)-β-D-galactosyl-(1→4)-β-D-glucosyl-(1↔1)-ceramide 4-β-D-galactosyltransferase

Links to other databases:

References:

Schwientek, T., Almeida, R., Levery, S.B., Holmes, E.H., Bennett, E. and Clausen, H. Cloning of a novel member of the UDP-galactose:β-N-acetylglucosamine β1,4-galactosyltransferase family, β4Gal-T4, involved in glycosphingolipid biosynthesis. J. Biol. Chem. 273 (1998) 29331–29340. [DOI] [PMID: 9792633]

[EC 2.4.1.275 created 2011, modified 2013]

2.4.1.276

Accepted name:

zeaxanthin glucosyltransferase

Reaction:

2 UDP-glucose + zeaxanthin = 2 UDP + zeaxanthin bis(β-D-glucoside)

For diagram of zeaxanthin biosynthesis, click here

Other name(s):

crtX (gene name)

Systematic name:

UDP-glucose:zeaxanthin β-D-glucosyltransferase

Comments:

The reaction proceeds in two steps with the monoglucoside as an intermediate.

Links to other databases:

References:

1.	Hundle, B.S., O'Brien, D.A., Alberti, M., Beyer, P. and Hearst, J.E. Functional expression of zeaxanthin glucosyltransferase from Erwinia herbicola and a proposed uridine diphosphate binding site. Proc. Natl. Acad. Sci. USA 89 (1992) 9321–9325. [DOI] [PMID: 1409639]

[EC 2.4.1.276 created 2011]

2.4.1.277

Accepted name:

10-deoxymethynolide desosaminyltransferase

Reaction:

dTDP-3-dimethylamino-3,4,6-trideoxy-α-D-glucopyranose + 10-deoxymethynolide = dTDP + 10-deoxymethymycin

For diagram of methymycin biosynthesis, click here and for diagram of pikromycin biosynthesis, click here

Glossary:

dTDP-3-dimethylamino-3,4,6-trideoxy-α-D-glucopyranose = dTDP-D-desosamine

Other name(s):

glycosyltransferase DesVII; DesVII

Systematic name:

dTDP-3-dimethylamino-3,4,6-trideoxy-α-D-glucopyranose:10-deoxymethynolide 3-dimethylamino-4,6-dideoxy-α-D-glucosyltransferase

Comments:

DesVII is the glycosyltransferase responsible for the attachment of dTDP-D-desosamine to 10-deoxymethynolide or narbonolide during the biosynthesis of methymycin, neomethymycin, narbomycin, and pikromycin in the bacterium Streptomyces venezuelae. Activity requires an additional protein partner, DesVIII.

Links to other databases:

References:

1.	Borisova, S.A. and Liu, H.W. Characterization of glycosyltransferase DesVII and its auxiliary partner protein DesVIII in the methymycin/picromycin biosynthetic pathway. Biochemistry 49 (2010) 8071–8084. [DOI] [PMID: 20695498]
2.	Borisova, S.A., Kim, H.J., Pu, X. and Liu, H.W. Glycosylation of acyclic and cyclic aglycone substrates by macrolide glycosyltransferase DesVII/DesVIII: analysis and implications. ChemBioChem 9 (2008) 1554–1558. [DOI] [PMID: 18548476]
3.	Hong, J.S., Park, S.J., Parajuli, N., Park, S.R., Koh, H.S., Jung, W.S., Choi, C.Y. and Yoon, Y.J. Functional analysis of DesVIII homologues involved in glycosylation of macrolide antibiotics by interspecies complementation. Gene 386 (2007) 123–130. [DOI] [PMID: 17049185]

[EC 2.4.1.277 created 2011, modified 2014]

*EC

2.4.99.12

Accepted name:

lipid IV_A 3-deoxy-D-manno-octulosonic acid transferase

Reaction:

CMP-β-Kdo + a lipid IV_A + CMP-β-Kdo = CMP + an α-Kdo-(2→6)-[lipid IV_A]

For diagram of Kdo₄-Lipid IV_A biosynthesis, click here

Glossary:

CMP-β-Kdo = CMP-3-deoxy-β-D-manno-octulosonate = CMP-3-deoxy-β-D-manno-oct-2-ulopyranosylonate
a lipid IV_A = 2-deoxy-2-{[(3R)-3-hydroxyacyl]amino}-3-O-[(3R)-3-hydroxyacyl]-4-O-phospho-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxyacyl]-2-{[(3R)-3-hydroxyacyl]amino}-1-O-phospho-α-D-glucopyranose

Other name(s):

waaA (gene name); kdtA (gene name); 3-deoxy-D-manno-oct-2-ulosonic acid transferase; 3-deoxy-manno-octulosonic acid transferase; lipid IV_A KDO transferase; CMP-3-deoxy-D-manno-oct-2-ulosonate:lipid IV_A 3-deoxy-D-manno-oct-2-ulosonate transferase; KDO transferase

Systematic name:

CMP-3-deoxy-β-D-manno-oct-2-ulosonate:[lipid IV_A] 3-deoxy-D-manno-oct-2-ulosonate transferase (configuration-inverting)

Comments:

The enzyme from Escherichia coli is bifunctional and transfers two 3-deoxy-D-manno-oct-2-ulosonate residues to lipid IV_A (cf. EC 2.4.99.13 [(Kdo)-lipid IV_A 3-deoxy-D-manno-octulosonic acid transferase]) [1]. The monofunctional enzymes from Bordetella pertusis, Aquifex aeolicus and Haemophilus influenzae catalyse the transfer of a single 3-deoxy-D-manno-oct-2-ulosonate residue from CMP-3-deoxy-D-manno-oct-2-ulosonate to lipid IV_A [2-4]. The enzymes from Chlamydia transfer three or more 3-deoxy-D-manno-oct-2-ulosonate residues and generate genus-specific epitopes [5].

Links to other databases:

References:

1.	Belunis, C.J. and Raetz, C.R. Biosynthesis of endotoxins. Purification and catalytic properties of 3-deoxy-D-manno-octulosonic acid transferase from Escherichia coli. J. Biol. Chem. 267 (1992) 9988–9997. [PMID: 1577828]
2.	Isobe, T., White, K.A., Allen, A.G., Peacock, M., Raetz, C.R. and Maskell, D.J. Bordetella pertussis waaA encodes a monofunctional 2-keto-3-deoxy-D-manno-octulosonic acid transferase that can complement an Escherichia coli waaA mutation. J. Bacteriol. 181 (1999) 2648–2651. [DOI] [PMID: 10198035]
3.	Mamat, U., Schmidt, H., Munoz, E., Lindner, B., Fukase, K., Hanuszkiewicz, A., Wu, J., Meredith, T.C., Woodard, R.W., Hilgenfeld, R., Mesters, J.R. and Holst, O. WaaA of the hyperthermophilic bacterium Aquifex aeolicus is a monofunctional 3-deoxy-D-manno-oct-2-ulosonic acid transferase involved in lipopolysaccharide biosynthesis. J. Biol. Chem. 284 (2009) 22248–22262. [DOI] [PMID: 19546212]
4.	White, K.A., Kaltashov, I.A., Cotter, R.J. and Raetz, C.R. A mono-functional 3-deoxy-D-manno-octulosonic acid (Kdo) transferase and a Kdo kinase in extracts of Haemophilus influenzae. J. Biol. Chem. 272 (1997) 16555–16563. [DOI] [PMID: 9195966]
5.	Lobau, S., Mamat, U., Brabetz, W. and Brade, H. Molecular cloning, sequence analysis, and functional characterization of the lipopolysaccharide biosynthetic gene kdtA encoding 3-deoxy-α-D-manno-octulosonic acid transferase of Chlamydia pneumoniae strain TW-183. Mol. Microbiol. 18 (1995) 391–399. [DOI] [PMID: 8748024]

[EC 2.4.99.12 created 2010, modified 2011]

*EC

2.4.99.13

Accepted name:

(Kdo)-lipid IV_A 3-deoxy-D-manno-octulosonic acid transferase

Reaction:

CMP-β-Kdo + an α-Kdo-(2→6)-[lipid IV_A] = CMP + an α-Kdo-(2→4)-α-Kdo-(2→6)-[lipid IV_A]

For diagram of Kdo₄-Lipid IV_A biosynthesis, click here

Glossary:

CMP-β-Kdo = CMP-3-deoxy-β-D-manno-oct-2-ulopyranosylonate
a lipid IV_A = 2-deoxy-2-{[(3R)-3-hydroxyacyl]amino}-3-O-[(3R)-3-hydroxyacyl]-4-O-phospho-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxyacyl]-2-{[(3R)-3-hydroxyacyl]amino}-1-O-phospho-α-D-glucopyranose

Other name(s):

waaA (gene name); kdtA (gene name); 3-deoxy-D-manno-oct-2-ulosonic acid transferase; 3-deoxy-manno-octulosonic acid transferase; (KDO)-lipid IV_A 3-deoxy-D-manno-octulosonic acid transferase; CMP-3-deoxy-D-manno-oct-2-ulosonate:(Kdo)-lipid IV_A 3-deoxy-D-manno-oct-2-ulosonate transferase; Kdo transferase (ambiguous)

Systematic name:

CMP-3-deoxy-β-D-manno-oct-2-ulosonate:α-Kdo-(2→6)-[lipid IV_A] 3-deoxy-D-manno-oct-2-ulosonate transferase (configuration-inverting)

Comments:

The enzyme from Escherichia coli is bifunctional and transfers two 3-deoxy-D-manno-oct-2-ulosonate residues to lipid IV_A (cf. EC 2.4.99.12 [lipid IV_A 3-deoxy-D-manno-octulosonic acid transferase]) [1]. The enzymes from Chlamydia transfer three or more 3-deoxy-D-manno-oct-2-ulosonate residues and generate genus-specific epitopes [2].

Links to other databases:

References:

1.	Belunis, C.J. and Raetz, C.R. Biosynthesis of endotoxins. Purification and catalytic properties of 3-deoxy-D-manno-octulosonic acid transferase from Escherichia coli. J. Biol. Chem. 267 (1992) 9988–9997. [PMID: 1577828]
2.	Lobau, S., Mamat, U., Brabetz, W. and Brade, H. Molecular cloning, sequence analysis, and functional characterization of the lipopolysaccharide biosynthetic gene kdtA encoding 3-deoxy-α-D-manno-octulosonic acid transferase of Chlamydia pneumoniae strain TW-183. Mol. Microbiol. 18 (1995) 391–399. [DOI] [PMID: 8748024]
3.	Schmidt, H., Hansen, G., Singh, S., Hanuszkiewicz, A., Lindner, B., Fukase, K., Woodard, R.W., Holst, O., Hilgenfeld, R., Mamat, U. and Mesters, J.R. Structural and mechanistic analysis of the membrane-embedded glycosyltransferase WaaA required for lipopolysaccharide synthesis. Proc. Natl. Acad. Sci. USA 109 (2012) 6253–6258. [DOI] [PMID: 22474366]

[EC 2.4.99.13 created 2010, modified 2011, modified 2021]

*EC

2.4.99.14

Accepted name:

(Kdo)₂-lipid IV_A (2-8) 3-deoxy-D-manno-octulosonic acid transferase

Reaction:

α-Kdo-(2→4)-α-Kdo-(2→6)-lipid IV_A + CMP-β-Kdo = α-Kdo-(2→8)-α-Kdo-(2→4)-α-Kdo-(2→6)-lipid IV_A + CMP

For diagram of Kdo₄-Lipid IV_A biosynthesis, click here

Glossary:

(Kdo)₂-lipid IV_A = α-Kdo-(2→4)-α-Kdo-(2→6)-lipid IV_A = (3-deoxy-α-D-manno-oct-2-ulopyranosylonate)-(2→4)-(3-deoxy-α-D-manno-oct-2-ulopyranosylonate)-(2→6)-2-deoxy-2-{[(3R)-3-hydroxytetradecanoyl]amino}-3-O-[(3R)-3-hydroxytetradecanoyl]-4-O-phosphono-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxytetradecanoyl]-2-{[(3R)-3-hydroxytetradecanoyl]amino}-1-O-phosphono-α-D-glucopyranose
(Kdo)₃-lipid IV_A = α-Kdo-(2→8)-α-Kdo-(2→4)-α-Kdo-(2→6)-lipid IV_A = (3-deoxy-α-D-manno-oct-2-ulopyranosylonate)-(2→8)-(3-deoxy-α-D-manno-oct-2-ulopyranosylonate)-(2→4)-(3-deoxy-α-D-manno-oct-2-ulopyranosylonate)-(2→6)-2-deoxy-2-{[(3R)-3-hydroxytetradecanoyl]amino}-3-O-[(3R)-3-hydroxytetradecanoyl]-4-O-phosphono-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxytetradecanoyl]-2-{[(3R)-3-hydroxytetradecanoyl]amino}-1-O-phosphono-α-D-glucopyranose
CMP-β-Kdo = CMP-3-deoxy-β-D-manno-oct-2-ulopyranosylonate

Other name(s):

Kdo transferase; waaA (gene name); kdtA (gene name); 3-deoxy-D-manno-oct-2-ulosonic acid transferase; 3-deoxy-manno-octulosonic acid transferase; (KDO)₂-lipid IV_A (2-8) 3-deoxy-D-manno-octulosonic acid transferase

Systematic name:

CMP-3-deoxy-D-manno-oct-2-ulosonate:(Kdo)₂-lipid IV_A 3-deoxy-D-manno-oct-2-ulosonate transferase [(2→8) glycosidic bond-forming]

Comments:

The enzymes from Chlamydia transfer three or more 3-deoxy-D-manno-oct-2-ulosonate residues and generate genus-specific epitopes.

Links to other databases:

References:

1.	Lobau, S., Mamat, U., Brabetz, W. and Brade, H. Molecular cloning, sequence analysis, and functional characterization of the lipopolysaccharide biosynthetic gene kdtA encoding 3-deoxy-α-D-manno-octulosonic acid transferase of Chlamydia pneumoniae strain TW-183. Mol. Microbiol. 18 (1995) 391–399. [DOI] [PMID: 8748024]
2.	Mamat, U., Baumann, M., Schmidt, G. and Brade, H. The genus-specific lipopolysaccharide epitope of Chlamydia is assembled in C. psittaci and C. trachomatis by glycosyltransferases of low homology. Mol. Microbiol. 10 (1993) 935–941. [DOI] [PMID: 7523826]
3.	Belunis, C.J., Mdluli, K.E., Raetz, C.R. and Nano, F.E. A novel 3-deoxy-D-manno-octulosonic acid transferase from Chlamydia trachomatis required for expression of the genus-specific epitope. J. Biol. Chem. 267 (1992) 18702–18707. [PMID: 1382060]

[EC 2.4.99.14 created 2010, modified 2011]

*EC

2.4.99.15

Accepted name:

(Kdo)₃-lipid IV_A (2-4) 3-deoxy-D-manno-octulosonic acid transferase

Reaction:

α-Kdo-(2→8)-α-Kdo-(2→4)-α-Kdo-(2→6)-lipid IV_A + CMP-β-Kdo = α-Kdo-(2→8)-[α-Kdo-(2→4)]-α-Kdo-(2→4)-α-Kdo-(2→6)-lipid IV_A + CMP

For diagram of Kdo₄-Lipid IV_A biosynthesis, click here

Glossary:

(Kdo)₃-lipid IV_A = α-Kdo-(2→8)-α-Kdo-(2→4)-α-Kdo-(2→6)-lipid IV_A = (3-deoxy-α-D-manno-oct-2-ulopyranosylonate)-(2→8)-(3-deoxy-α-D-manno-oct-2-ulopyranosylonate)-(2→4)-(3-deoxy-α-D-manno-oct-2-ulopyranosylonate)-(2→6)-2-deoxy-2-{[(3R)-3-hydroxytetradecanoyl]amino}-3-O-[(3R)-3-hydroxytetradecanoyl]-4-O-phosphono-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxytetradecanoyl]-2-{[(3R)-3-hydroxytetradecanoyl]amino}-1-O-phosphono-α-D-glucopyranose
(Kdo)₄-lipid IV_A = α-Kdo-(2→8)-[α-Kdo-(2→4)]-α-Kdo-(2→4)-α-Kdo-(2→6)-lipid IV_A = (3-deoxy-α-D-manno-oct-2-ulopyranosylonate)-(2→8)-[(3-deoxy-α-D-manno-oct-2-ulopyranosylonate)-(2→4)]-(3-deoxy-α-D-manno-oct-2-ulopyranosylonate)-(2→4)-(3-deoxy-α-D-manno-oct-2-ulopyranosylonate)-(2→6)-2-deoxy-2-{[(3R)-3-hydroxytetradecanoyl]amino}-3-O-[(3R)-3-hydroxytetradecanoyl]-4-O-phosphono-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxytetradecanoyl]-2-{[(3R)-3-hydroxytetradecanoyl]amino}-1-O-phosphono-α-D-glucopyranose
CMP-β-Kdo = CMP-3-deoxy-β-D-manno-oct-2-ulopyranosylonate

Other name(s):

Kdo transferase; waaA (gene name); kdtA (gene name); 3-deoxy-D-manno-oct-2-ulosonic acid transferase; 3-deoxy-manno-octulosonic acid transferase; (KDO)₃-lipid IV_A (2-4) 3-deoxy-D-manno-octulosonic acid transferase

Systematic name:

CMP-3-deoxy-D-manno-oct-2-ulosonate:(Kdo)₃-lipid IV_A 3-deoxy-D-manno-oct-2-ulosonate transferase [(2→4) glycosidic bond-forming]

Comments:

The enzyme from Chlamydia psittaci transfers four Kdo residues to lipid A, forming a branched tetrasaccharide with the structure α-Kdo-(2,8)-[α-Kdo-(2,4)]-α-Kdo-(2,4)-α-Kdo (cf. EC 2.4.99.12 [lipid IV_A 3-deoxy-D-manno-octulosonic acid transferase], EC 2.4.99.13 [(Kdo)-lipid IV_A 3-deoxy-D-manno-octulosonic acid transferase], and EC 2.4.99.14 [(Kdo)₂-lipid IV_A (2-8) 3-deoxy-D-manno-octulosonic acid transferase]).

Links to other databases:

References:

1.	Brabetz, W., Lindner, B. and Brade, H. Comparative analyses of secondary gene products of 3-deoxy-D-manno-oct-2-ulosonic acid transferases from Chlamydiaceae in Escherichia coli K-12. Eur. J. Biochem. 267 (2000) 5458–5465. [DOI] [PMID: 10951204]
2.	Holst, O., Bock, K., Brade, L. and Brade, H. The structures of oligosaccharide bisphosphates isolated from the lipopolysaccharide of a recombinant Escherichia coli strain expressing the gene gseA [3-deoxy-D-manno-octulopyranosonic acid (Kdo) transferase] of Chlamydia psittaci 6BC. Eur. J. Biochem. 229 (1995) 194–200. [DOI] [PMID: 7744029]

[EC 2.4.99.15 created 2010, modified 2011]

2.5.1.95

Accepted name:

xanthan ketal pyruvate transferase

Reaction:

phosphoenolpyruvate + D-Man-β-(1→4)-D-GlcA-β-(1→2)-D-Man-α-(1→3)-D-Glc-β-(1→4)-D-Glc-α-1-diphospho-ditrans,octacis-undecaprenol = 4,6-CH₃(COO^-)C-D-Man-β-(1→4)-D-GlcA-β-(1→2)-D-Man-α-(1→3)-D-Glc-β-(1→4)-D-Glc-α-1-diphospho-ditrans,octacis-undecaprenol + phosphate

For diagram of xanthan biosynthesis, click here

Other name(s):

KPT

Systematic name:

phosphoenolpyruvate:D-Man-β-(1→4)-GlcA-β-(1→2)-D-Man-α-(1→3)-D-Glc-β-(1→4)-D-Glc-α-1-diphospho-ditrans,octacis-undecaprenol 4,6-O-(1-carboxyethan-1,1-diyl)transferase

Comments:

Involved in the biosynthesis of the polysaccharide xanthan. 30-40% of the terminal mannose residues of xanthan have a 4,6-O-(1-carboxyethan-1,1-diyl) ketal group. It also acts on the 6-O-acetyl derivative of the inner mannose unit.

Links to other databases:

References:

1.	Marzocca, M.P., Harding, N.E., Petroni, E.A., Cleary, J.M. and Ielpi, L. Location and cloning of the ketal pyruvate transferase gene of Xanthomonas campestris. J. Bacteriol. 173 (1991) 7519–7524. [DOI] [PMID: 1657892]

[EC 2.5.1.95 created 2011, modified 2012]

2.5.1.96

Accepted name:

4,4′-diapophytoene synthase

Reaction:

2 (2E,6E)-farnesyl diphosphate = 15-cis-4,4′-diapophytoene + 2 diphosphate (overall reaction)
(1a) 2 (2E,6E)-farnesyl diphosphate = diphosphate + presqualene diphosphate
(1b) presqualene diphosphate = 15-cis-4,4′-diapophytoene + diphosphate

For diagram of squalene, phytoene and 4,4′-diapophytoene biosynthesis, click here

Other name(s):

dehydrosqualene synthase; DAP synthase; C₃₀ carotene synthase; CrtM

Systematic name:

farnesyl-diphosphate:farnesyl-diphosphate farnesyltransferase (15-cis-4,4′-diapophytoene-forming)

Comments:

Requires Mn²⁺. Typical of Staphylococcus aureus and some other bacteria such as Heliobacillus sp.

Links to other databases:

References:

1.	Umeno, D., Tobias, A.V. and Arnold, F.H. Evolution of the C₃₀ carotenoid synthase CrtM for function in a C₄₀ pathway. J. Bacteriol. 184 (2002) 6690–6699. [DOI] [PMID: 12426357]
2.	Pelz, A., Wieland, K.P., Putzbach, K., Hentschel, P., Albert, K. and Gotz, F. Structure and biosynthesis of staphyloxanthin from Staphylococcus aureus. J. Biol. Chem. 280 (2005) 32493–32498. [DOI] [PMID: 16020541]
3.	Ku, B., Jeong, J.C., Mijts, B.N., Schmidt-Dannert, C. and Dordick, J.S. Preparation, characterization, and optimization of an in vitro C₃₀ carotenoid pathway. Appl. Environ. Microbiol. 71 (2005) 6578–6583. [DOI] [PMID: 16269684]
4.	Liu, C.I., Liu, G.Y., Song, Y., Yin, F., Hensler, M.E., Jeng, W.Y., Nizet, V., Wang, A.H. and Oldfield, E. A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence. Science 319 (2008) 1391–1394. [DOI] [PMID: 18276850]

[EC 2.5.1.96 created 2011]

2.5.1.97

Accepted name:

pseudaminic acid synthase

Reaction:

phosphoenolpyruvate + 2,4-bis(acetylamino)-2,4,6-trideoxy-β-L-altropyranose + H₂O = 5,7-bis(acetylamino)-3,5,7,9-tetradeoxy-L-glycero-α-L-manno-2-nonulopyranosonic acid + phosphate

Glossary:

pseudaminic acid = 5,7-bis(acetylamino)-3,5,7,9-tetradeoxy-L-glycero-α-L-manno-2-nonulopyranosonic acid

Other name(s):

PseI; NeuB3

Systematic name:

phosphoenolpyruvate:2,4-bis(acetylamino)-2,4,6-trideoxy-β-L-altropyranose transferase (phosphate-hydrolysing, 2,7-acetylamino-transfering, 2-carboxy-2-oxoethyl-forming)

Comments:

The enzyme requires a divalent metal ion, the highest activity values are observed in the presence of Mn²⁺ and Co²⁺ (10 mM).

Links to other databases:

References:

1.	Chou, W.K., Dick, S., Wakarchuk, W.W. and Tanner, M.E. Identification and characterization of NeuB3 from Campylobacter jejuni as a pseudaminic acid synthase. J. Biol. Chem. 280 (2005) 35922–35928. [DOI] [PMID: 16120604]

[EC 2.5.1.97 created 2011]

2.6.1.88

Accepted name:

methionine transaminase

Reaction:

L-methionine + a 2-oxo carboxylate = 4-(methylsulfanyl)-2-oxobutanoate + an L-amino acid

Other name(s):

methionine-oxo-acid transaminase

Systematic name:

L-methionine:2-oxo-acid aminotransferase

Comments:

The enzyme is most active with L-methionine. It participates in the L-methionine salvage pathway from S-methyl-5′-thioadenosine, a by-product of polyamine biosynthesis. The enzyme from the bacterium Klebsiella pneumoniae can use several different amino acids as amino donor, with aromatic amino acids being the most effective [1]. The enzyme from the plant Arabidopsis thaliana is also a part of the chain elongation pathway in the biosynthesis of methionine-derived glucosinolates [3].

Links to other databases:

References:

1.	Heilbronn, J., Wilson, J. and Berger, B.J. Tyrosine aminotransferase catalyzes the final step of methionine recycling in Klebsiella pneumoniae. J. Bacteriol. 181 (1999) 1739–1747. [PMID: 10074065]
2.	Dolzan, M., Johansson, K., Roig-Zamboni, V., Campanacci, V., Tegoni, M., Schneider, G. and Cambillau, C. Crystal structure and reactivity of YbdL from Escherichia coli identify a methionine aminotransferase function. FEBS Lett. 571 (2004) 141–146. [DOI] [PMID: 15280032]
3.	Schuster, J., Knill, T., Reichelt, M., Gershenzon, J. and Binder, S. Branched-chain aminotransferase4 is part of the chain elongation pathway in the biosynthesis of methionine-derived glucosinolates in Arabidopsis. Plant Cell 18 (2006) 2664–2679. [DOI] [PMID: 17056707]

[EC 2.6.1.88 created 2011]

2.6.1.89

Accepted name:

dTDP-3-amino-3,6-dideoxy-α-D-glucopyranose transaminase

Reaction:

dTDP-3-amino-3,6-dideoxy-α-D-glucopyranose + 2-oxoglutarate = dTDP-3-dehydro-6-deoxy-α-D-glucopyranose + L-glutamate

For diagram of dTDP-D-mycaminose biosynthesis, click here

Glossary:

dTDP-D-mycaminose = dTDP-3-dimethylamino-3,6-dideoxy-α-D-glucopyranose

Other name(s):

TylB; TDP-3-keto-6-deoxy-D-glucose 3-aminotransferase; TDP-3-dehydro-6-deoxy-D-glucose 3-aminotransferase; dTDP-3-keto-6-deoxy-D-glucose 3-aminotransferase; dTDP-3-dehydro-6-deoxy-D-glucose 3-aminotransferase

Systematic name:

dTDP-3-amino-3,6-dideoxy-α-D-glucopyranose:2-oxoglutarate aminotransferase

Comments:

A pyridoxal-phosphate protein. The reaction occurs in the reverse direction. The enzyme is involved in biosynthesis of D-mycaminose.

Links to other databases:

References:

Melancon, C.E., 3rd, Hong, L., White, J.A., Liu, Y.N. and Liu, H.W. Characterization of TDP-4-keto-6-deoxy-D-glucose-3,4-ketoisomerase from the D-mycaminose biosynthetic pathway of Streptomyces fradiae: in vitro activity and substrate specificity studies. Biochemistry 46 (2007) 577–590. [DOI] [PMID: 17209568]

[EC 2.6.1.89 created 2011]

2.6.1.90

Accepted name:

dTDP-3-amino-3,6-dideoxy-α-D-galactopyranose transaminase

Reaction:

dTDP-3-amino-3,6-dideoxy-α-D-galactopyranose + 2-oxoglutarate = dTDP-3-dehydro-6-deoxy-α-D-galactopyranose + L-glutamate

For diagram of dTDP-Fuc3NAc and dTDP-Fuc4NAc biosynthesis, click here

Glossary:

dTDP-3-dehydro-6-deoxy-D-galactopyranose = dTDP-6-deoxy-D-xylo-hexopyranos-3-ulose

Other name(s):

dTDP-6-deoxy-D-xylohex-3-uloseaminase; FdtB; TDP-3-keto-6-deoxy-D-galactose-3-aminotransferase; RavAMT; TDP-3-keto-6-deoxy-D-galactose 3-aminotransferase; TDP-3-dehydro-6-deoxy-D-galactose 3-aminotransferase

Systematic name:

dTDP-3-amino-3,6-dideoxy-α-D-galactopyranose:2-oxoglutarate aminotransferase

Comments:

A pyridoxal-phosphate protein. The enzyme is involved in the biosynthesis of dTDP-3-acetamido-3,6-dideoxy-α-D-galactose. The reaction occurs in the reverse direction.

Links to other databases:

References:

1.	Pfoestl, A., Hofinger, A., Kosma, P. and Messner, P. Biosynthesis of dTDP-3-acetamido-3,6-dideoxy-α-D-galactose in Aneurinibacillus thermoaerophilus L420-91^T. J. Biol. Chem. 278 (2003) 26410–26417. [DOI] [PMID: 12740380]

[EC 2.6.1.90 created 2011]

2.6.1.91

Deleted entry:

UDP-4-amino-4,6-dideoxy-N-acetyl-α-D-glucosamine transaminase. Identical to EC 2.6.1.34, UDP-N-acetylbacillosamine transaminase.

[EC 2.6.1.91 created 2011, deleted 2013]

2.6.1.92

Accepted name:

UDP-4-amino-4,6-dideoxy-N-acetyl-β-L-altrosamine transaminase

Reaction:

UDP-4-amino-4,6-dideoxy-N-acetyl-β-L-altrosamine + 2-oxoglutarate = UDP-2-acetamido-2,6-dideoxy-β-L-arabino-hex-4-ulose + L-glutamate

Other name(s):

PseC; UDP-4-amino-4,6-dideoxy-N-acetyl-β-L-altrosamine:2-oxoglutarate aminotransferase; UDP-β-L-threo-pentapyranos-4-ulose transaminase; UDP-4-dehydro-6-deoxy-D-glucose transaminase

Systematic name:

UDP-4-amino-4,6-dideoxy-N-acetyl-β-L-altrosamine:2-oxoglutarate transaminase

Comments:

A pyridoxal 5′-phosphate protein. The enzyme transfers the primary amino group of L-glutamate to C-4′′ of UDP-4-dehydro sugars, forming a C-N bond in a stereo configuration opposite to that of UDP. The enzyme from the bacterium Bacillus cereus has been shown to act on UDP-2-acetamido-2,6-dideoxy-β-L-arabino-hex-4-ulose, UDP-β-L-threo-pentapyranos-4-ulose, UDP-4-dehydro-6-deoxy-D-glucose, and UDP-2-acetamido-2,6-dideoxy-α-D-xylo-hex-4-ulose. cf. EC 2.6.1.34, UDP-N-acetylbacillosamine transaminase, which catalyses a similar reaction, but forms the C-N bond in the same stereo configuration as that of UDP.

Links to other databases:

References:

1.	Schoenhofen, I.C., McNally, D.J., Vinogradov, E., Whitfield, D., Young, N.M., Dick, S., Wakarchuk, W.W., Brisson, J.R. and Logan, S.M. Functional characterization of dehydratase/aminotransferase pairs from Helicobacter and Campylobacter: enzymes distinguishing the pseudaminic acid and bacillosamine biosynthetic pathways. J. Biol. Chem. 281 (2006) 723–732. [DOI] [PMID: 16286454]
2.	Schoenhofen, I.C., Lunin, V.V., Julien, J.P., Li, Y., Ajamian, E., Matte, A., Cygler, M., Brisson, J.R., Aubry, A., Logan, S.M., Bhatia, S., Wakarchuk, W.W. and Young, N.M. Structural and functional characterization of PseC, an aminotransferase involved in the biosynthesis of pseudaminic acid, an essential flagellar modification in Helicobacter pylori. J. Biol. Chem. 281 (2006) 8907–8916. [DOI] [PMID: 16421095]
3.	Mostafavi, A.Z. and Troutman, J.M. Biosynthetic assembly of the Bacteroides fragilis capsular polysaccharide A precursor bactoprenyl diphosphate-linked acetamido-4-amino-6-deoxygalactopyranose. Biochemistry 52 (2013) 1939–1949. [DOI] [PMID: 23458065]
4.	Hwang, S., Li, Z., Bar-Peled, Y., Aronov, A., Ericson, J. and Bar-Peled, M. The biosynthesis of UDP-D-FucNAc-4N-2-oxoglutarate (UDP-Yelosamine) in Bacillus cereus ATCC 14579: Pat and Pyl, an aminotransferase and an ATP-dependent Grasp protein that ligates 2-oxoglutarate to UDP-4-amino-sugars. J. Biol. Chem. 289 (2014) 35620–35632. [DOI] [PMID: 25368324]

[EC 2.6.1.92 created 2011, modified 2018]

*EC

2.7.1.61

Accepted name:

acyl-phosphate—hexose phosphotransferase

Reaction:

acyl phosphate + D-hexose = a carboxylate + D-hexose phosphate

Other name(s):

hexose phosphate:hexose phosphotransferase

Systematic name:

acyl-phosphate:D-hexose phosphotransferase

Comments:

Phosphorylates D-glucose and D-mannose on O-6, and D-fructose on O-1 or O-6.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 37278-06-1

References:

1.	Anderson, R.L. and Kamel, M.Y. Acyl phosphate:hexose phosphotransferase (hexose phosphate:hexose phosphotransferase). Methods Enzymol. 9 (1966) 392–396.
2.	Kamel, M.Y. and Anderson, R.L. Acyl phosphate: hexose phosphotransferase. Purification and properties of the enzyme from Aerobacter aerogenes and evidence for its common identity with hexose phosphate: hexose phosphotransferase. Arch. Biochem. Biophys. 120 (1967) 322–331. [DOI] [PMID: 6033450]
3.	Casazza, J.P. and Fromm, H.J. Purification and initial rate kinetics of acyl-phosphate-hexose phosphotransferase from Aerobacter aerogenes. Biochemistry 16 (1977) 3091–3097. [PMID: 196625]

[EC 2.7.1.61 created 1972, modified 2011]

*EC

2.7.1.119

Accepted name:

hygromycin-B 7′′-O-kinase

Reaction:

ATP + hygromycin B = ADP + 7′′-O-phosphohygromycin B

For diagram click here

Other name(s):

hygromycin B phosphotransferase; hygromycin-B kinase (ambiguous)

Systematic name:

ATP:hygromycin-B 7′′-O-phosphotransferase

Comments:

Phosphorylates the antibiotics hygromycin B, 1-N-hygromycin B and destomycin, but not hygromycin B2, at the 7′′-hydroxy group in the destomic acid ring.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 88361-67-5

References:

1.	Zalacain, M., Pardo, J.M. and Jiménez, A. Purification and characterization of a hygromycin B phosphotransferase from Streptomyces hygroscopicus. Eur. J. Biochem. 162 (1987) 419–422. [DOI] [PMID: 3026811]

[EC 2.7.1.119 created 1989, modified 2009, modified 2011]

*EC

2.7.1.166

Accepted name:

3-deoxy-D-manno-octulosonic acid kinase

Reaction:

α-Kdo-(2→6)-lipid IV_A + ATP = 4-O-phospho-α-Kdo-(2→6)-lipid IV_A + ADP

Glossary:

(Kdo)-lipid IV_A = α-Kdo-(2→6)-lipid IV_A = (3-deoxy-α-D-manno-oct-2-ulopyranosylonate)-(2→6)-2-deoxy-2-{[(3R)-3-hydroxytetradecanoyl]amino}-3-O-[(3R)-3-hydroxytetradecanoyl]-4-O-phosphono-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxytetradecanoyl]-2-{[(3R)-3-hydroxytetradecanoyl]amino}-1-O-phosphono-α-D-glucopyranose
(4-O-phospho-KDO)-lipid IV_A = 4-O-phospho-α-Kdo-(2→6)-lipid IV_A = (3-deoxy-4-O-phosphono-α-D-manno-oct-2-ulopyranosylonate)-(2→6)-2-deoxy-2-{[(3R)-3-hydroxytetradecanoyl]amino}-3-O-[(3R)-3-hydroxytetradecanoyl]-4-O-phosphono-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxytetradecanoyl]-2-{[(3R)-3-hydroxytetradecanoyl]amino}-1-O-phosphono-α-D-glucopyranose

Other name(s):

kdkA (gene name); Kdo kinase

Systematic name:

ATP:(Kdo)-lipid IV_A 3-deoxy-α-D-manno-oct-2-ulopyranose 4-phosphotransferase

Comments:

The enzyme phosphorylates the 4-OH position of Kdo in (Kdo)-lipid IV_A.

Links to other databases:

References:

1.	Brabetz, W., Muller-Loennies, S. and Brade, H. 3-Deoxy-D-manno-oct-2-ulosonic acid (Kdo) transferase (WaaA) and kdo kinase (KdkA) of Haemophilus influenzae are both required to complement a waaA knockout mutation of Escherichia coli. J. Biol. Chem. 275 (2000) 34954–34962. [DOI] [PMID: 10952982]
2.	Harper, M., Boyce, J.D., Cox, A.D., St Michael, F., Wilkie, I.W., Blackall, P.J. and Adler, B. Pasteurella multocida expresses two lipopolysaccharide glycoforms simultaneously, but only a single form is required for virulence: identification of two acceptor-specific heptosyl I transferases. Infect. Immun. 75 (2007) 3885–3893. [DOI] [PMID: 17517879]
3.	White, K.A., Kaltashov, I.A., Cotter, R.J. and Raetz, C.R. A mono-functional 3-deoxy-D-manno-octulosonic acid (Kdo) transferase and a Kdo kinase in extracts of Haemophilus influenzae. J. Biol. Chem. 272 (1997) 16555–16563. [DOI] [PMID: 9195966]
4.	White, K.A., Lin, S., Cotter, R.J. and Raetz, C.R. A Haemophilus influenzae gene that encodes a membrane bound 3-deoxy-D-manno-octulosonic acid (Kdo) kinase. Possible involvement of kdo phosphorylation in bacterial virulence. J. Biol. Chem. 274 (1999) 31391–31400. [DOI] [PMID: 10531340]

[EC 2.7.1.166 created 2010, modified 2011]

*EC

2.7.1.170

Accepted name:

anhydro-N-acetylmuramic acid kinase

Reaction:

ATP + 1,6-anhydro-N-acetyl-β-muramate + H₂O = ADP + N-acetylmuramate 6-phosphate

Other name(s):

anhMurNAc kinase; AnmK

Systematic name:

ATP:1,6-anhydro-N-acetyl-β-muramate 6-phosphotransferase

Comments:

This enzyme, along with EC 4.2.1.126, N-acetylmuramic acid 6-phosphate etherase, is required for the utilization of anhydro-N-acetylmuramic acid in proteobacteria. The substrate is either imported from the medium or derived from the bacterium’s own cell wall murein during cell wall recycling. The product N-acetylmuramate 6-phosphate is produced as a 7:1 mixture of the α- and β-anomers.

Links to other databases:

References:

1.	Uehara, T., Suefuji, K., Valbuena, N., Meehan, B., Donegan, M. and Park, J.T. Recycling of the anhydro-N-acetylmuramic acid derived from cell wall murein involves a two-step conversion to N-acetylglucosamine-phosphate. J. Bacteriol. 187 (2005) 3643–3649. [DOI] [PMID: 15901686]
2.	Uehara, T., Suefuji, K., Jaeger, T., Mayer, C. and Park, J.T. MurQ etherase is required by Escherichia coli in order to metabolize anhydro-N-acetylmuramic acid obtained either from the environment or from its own cell wall. J. Bacteriol. 188 (2006) 1660–1662. [DOI] [PMID: 16452451]
3.	Bacik, J.P., Whitworth, G.E., Stubbs, K.A., Yadav, A.K., Martin, D.R., Bailey-Elkin, B.A., Vocadlo, D.J. and Mark, B.L. Molecular basis of 1,6-anhydro bond cleavage and phosphoryl transfer by Pseudomonas aeruginosa 1,6-anhydro-N-acetylmuramic acid kinase. J. Biol. Chem. 286 (2011) 12283–12291. [DOI] [PMID: 21288904]

[EC 2.7.1.170 created 2011, modified 2011]

2.7.7.77

Accepted name:

molybdenum cofactor guanylyltransferase

Reaction:

GTP + molybdenum cofactor = diphosphate + guanylyl molybdenum cofactor

For diagram of MoCo biosynthesis, click here

Glossary:

molybdenum cofactor = MoCo = MoO2(OH)Dtpp-mP = {[(5aR,8R,9aR)-2-amino-4-oxo-6,7-bis(sulfanyl-κS)-1,5,5a,8,9a,10-hexahydro-4H-pyrano[3,2-g]pteridin-8-yl]methyl dihydrogenato(2^-) phosphate}(dioxo)molybdate

Other name(s):

MobA; MoCo guanylyltransferase

Systematic name:

GTP:molybdenum cofactor guanylyltransferase

Comments:

Catalyses the guanylation of the molybdenum cofactor. This modification occurs only in prokaryotes.

Links to other databases:

References:

1.	Lake, M.W., Temple, C.A., Rajagopalan, K.V. and Schindelin, H. The crystal structure of the Escherichia coli MobA protein provides insight into molybdopterin guanine dinucleotide biosynthesis. J. Biol. Chem. 275 (2000) 40211–40217. [DOI] [PMID: 10978347]
2.	Temple, C.A. and Rajagopalan, K.V. Mechanism of assembly of the bis(molybdopterin guanine dinucleotide)molybdenum cofactor in Rhodobacter sphaeroides dimethyl sulfoxide reductase. J. Biol. Chem. 275 (2000) 40202–40210. [DOI] [PMID: 10978348]
3.	Guse, A., Stevenson, C.E., Kuper, J., Buchanan, G., Schwarz, G., Giordano, G., Magalon, A., Mendel, R.R., Lawson, D.M. and Palmer, T. Biochemical and structural analysis of the molybdenum cofactor biosynthesis protein MobA. J. Biol. Chem. 278 (2003) 25302–25307. [DOI] [PMID: 12719427]

[EC 2.7.7.77 created 2011]

2.7.7.78

Accepted name:

GDP-D-glucose phosphorylase

Reaction:

GDP-α-D-glucose + phosphate = α-D-glucose 1-phosphate + GDP

Systematic name:

GDP:α-D-glucose 1-phosphate guanylyltransferase

Comments:

The enzyme may be involved in prevention of misincorporation of glucose in place of mannose residues into glycoconjugates i.e. to remove accidentally produced GDP-α-D-glucose. Activities with GDP-L-galactose, GDP-D-mannose and UDP-D-glucose are all less than 3% that with GDP-D-glucose.

Links to other databases:

References:

1.	El Yacoubi, B., Lyons, B., Cruz, Y., Reddy, R., Nordin, B., Agnelli, F., Williamson, J.R., Schimmel, P., Swairjo, M.A. and de Crecy-Lagard, V. The universal YrdC/Sua5 family is required for the formation of threonylcarbamoyladenosine in tRNA. Nucleic Acids Res. 37 (2009) 2894–2909. [DOI] [PMID: 19287007]
2.	Harris, K.A., Jones, V., Bilbille, Y., Swairjo, M.A. and Agris, P.F. YrdC exhibits properties expected of a subunit for a tRNA threonylcarbamoyl transferase. RNA 17 (2011) 1678–1687. [DOI] [PMID: 21775474]
3.	Kuratani, M., Kasai, T., Akasaka, R., Higashijima, K., Terada, T., Kigawa, T., Shinkai, A., Bessho, Y. and Yokoyama, S. Crystal structure of Sulfolobus tokodaii Sua5 complexed with L-threonine and AMPPNP. Proteins 79 (2011) 2065–2075. [DOI] [PMID: 21538543]
4.	Lauhon, C.T. Mechanism of N⁶-threonylcarbamoyladenonsine (t⁶A) biosynthesis: isolation and characterization of the intermediate threonylcarbamoyl-AMP. Biochemistry 51 (2012) 8950–8963. [DOI] [PMID: 23072323]
5.	Deutsch, C., El Yacoubi, B., de Crecy-Lagard, V. and Iwata-Reuyl, D. Biosynthesis of threonylcarbamoyl adenosine (t⁶A), a universal tRNA nucleoside. J. Biol. Chem. 287 (2012) 13666–13673. [DOI] [PMID: 22378793]
6.	Perrochia, L., Crozat, E., Hecker, A., Zhang, W., Bareille, J., Collinet, B., van Tilbeurgh, H., Forterre, P. and Basta, T. In vitro biosynthesis of a universal t⁶A tRNA modification in Archaea and Eukarya. Nucleic Acids Res. 41 (2013) 1953–1964. [DOI] [PMID: 23258706]
7.	Wan, L.C.K., Mao, D.Y.L., Neculai, D., Strecker, J., Chiovitti, D., Kurinov, I., Poda, G., Thevakumaran, N., Yuan, F., Szilard, R.K., Lissina, E., Nislow, C., Caudy, A.A., Durocher, D. and Sicheri, F. Reconstitution and characterization of eukaryotic N⁶-threonylcarbamoylation of tRNA using a minimal enzyme system. Nucleic Acids Res. 41 (2013) 6332–6346. [DOI] [PMID: 23620299]

[EC 2.7.7.78 created 2011]

2.7.7.79

Accepted name:

tRNA^His guanylyltransferase

Reaction:

p-tRNA^His + ATP + GTP + H₂O = pGp-tRNA^His + AMP + 2 diphosphate (overall reaction)
(1a) p-tRNA^His + ATP = App-tRNA^His + diphosphate
(1b) App-tRNA^His + GTP = pppGp-tRNA^His + AMP
(1c) pppGp-tRNA^His + H₂O = pGp-tRNA^His + diphosphate

Glossary:

p-tRNA^His = 5′-phospho-ribonucleotide-[tRNA^His]
pGp-tRNA^His = 5′-phospho-guanosine-ribonucleotide-[tRNA^His]
App-tRNA^His = 5′-(5′-diphosphoadenosine)-ribonucleotide-[tRNA^His]
pppGp-tRNA^His = 5′-triphospho-ribonucleotide-[tRNA^His]

Other name(s):

histidine tRNA guanylyltransferase; Thg1p (ambiguous); Thg1 (ambiguous)

Systematic name:

p-tRNA^His:GTP guanylyltransferase (ATP-hydrolysing)

Comments:

In eukarya an additional guanosine residue is added post-transcriptionally to the 5′-end of tRNA^His molecules. The addition occurs opposite a universally conserved adenosine⁷³ and is thus the result of a non-templated 3′-5′ addition reaction. The additional guanosine residue is an important determinant for aminoacylation by EC 6.1.1.21, histidine—tRNA ligase.The enzyme requires a divalent cation for activity [2]. ATP activation is not required when the substrate contains a 5′-triphosphate (ppp-tRNA^His) [3].

Links to other databases:

References:

1.	Jahn, D. and Pande, S. Histidine tRNA guanylyltransferase from Saccharomyces cerevisiae. II. Catalytic mechanism. J. Biol. Chem. 266 (1991) 22832–22836. [PMID: 1660462]
2.	Pande, S., Jahn, D. and Soll, D. Histidine tRNA guanylyltransferase from Saccharomyces cerevisiae. I. Purification and physical properties. J. Biol. Chem. 266 (1991) 22826–22831. [PMID: 1660461]
3.	Gu, W., Jackman, J.E., Lohan, A.J., Gray, M.W. and Phizicky, E.M. tRNA^His maturation: an essential yeast protein catalyzes addition of a guanine nucleotide to the 5′ end of tRNA^His. Genes Dev. 17 (2003) 2889–2901. [DOI] [PMID: 14633974]
4.	Placido, A., Sieber, F., Gobert, A., Gallerani, R., Giege, P. and Marechal-Drouard, L. Plant mitochondria use two pathways for the biogenesis of tRNA^His. Nucleic Acids Res. 38 (2010) 7711–7717. [DOI] [PMID: 20660484]
5.	Jackman, J.E. and Phizicky, E.M. Identification of critical residues for G-1 addition and substrate recognition by tRNA(His) guanylyltransferase. Biochemistry 47 (2008) 4817–4825. [DOI] [PMID: 18366186]
6.	Hyde, S.J., Eckenroth, B.E., Smith, B.A., Eberley, W.A., Heintz, N.H., Jackman, J.E. and Doublie, S. tRNA(His) guanylyltransferase (THG1), a unique 3′-5′ nucleotidyl transferase, shares unexpected structural homology with canonical 5′-3′ DNA polymerases. Proc. Natl. Acad. Sci. USA 107 (2010) 20305–20310. [DOI] [PMID: 21059936]

[EC 2.7.7.79 created 2011]

2.7.7.80

Accepted name:

molybdopterin-synthase adenylyltransferase

Reaction:

ATP + [molybdopterin-synthase sulfur-carrier protein]-Gly-Gly = diphosphate + [molybdopterin-synthase sulfur-carrier protein]-Gly-Gly-AMP

For diagram of MoCo biosynthesis, click here

Glossary:

small subunit of the molybdopterin synthase = molybdopterin-synthase sulfur-carrier protein = MoaD

Other name(s):

MoeB; adenylyltransferase and sulfurtransferase MOCS3

Systematic name:

ATP:molybdopterin-synthase adenylyltransferase

Comments:

Adenylates the C-terminus of the small subunit of the molybdopterin synthase. This activation is required to form the thiocarboxylated C-terminus of the active molybdopterin synthase small subunit. The reaction occurs in prokaryotes and eukaryotes. In the human, the reaction is catalysed by the N-terminal domain of the protein MOCS3, which also includes a molybdopterin-synthase sulfurtransferase (EC 2.8.1.11) C-terminal domain.

Links to other databases:

References:

1.	Leimkuhler, S., Wuebbens, M.M. and Rajagopalan, K.V. Characterization of Escherichia coli MoeB and its involvement in the activation of molybdopterin synthase for the biosynthesis of the molybdenum cofactor. J. Biol. Chem. 276 (2001) 34695–34701. [DOI] [PMID: 11463785]
2.	Matthies, A., Nimtz, M. and Leimkuhler, S. Molybdenum cofactor biosynthesis in humans: identification of a persulfide group in the rhodanese-like domain of MOCS3 by mass spectrometry. Biochemistry 44 (2005) 7912–7920. [DOI] [PMID: 15910006]

[EC 2.7.7.80 created 2011]

*EC

2.8.1.7

Accepted name:

cysteine desulfurase

Reaction:

L-cysteine + acceptor = L-alanine + S-sulfanyl-acceptor (overall reaction)
(1a) L-cysteine + [enzyme]-cysteine = L-alanine + [enzyme]-S-sulfanylcysteine
(1b) [enzyme]-S-sulfanylcysteine + acceptor = [enzyme]-cysteine + S-sulfanyl-acceptor

For diagram of MoCo biosynthesis, click here

Other name(s):

IscS; NIFS; NifS; SufS; cysteine desulfurylase

Systematic name:

L-cysteine:acceptor sulfurtransferase

Comments:

A pyridoxal-phosphate protein. The sulfur from free L-cysteine is first transferred to a cysteine residue in the active site, and then passed on to various other acceptors. The enzyme is involved in the biosynthesis of iron-sulfur clusters, thio-nucleosides in tRNA, thiamine, biotin, lipoate and pyranopterin (molybdopterin) [2]. In Azotobacter vinelandii, this sulfur provides the inorganic sulfide required for nitrogenous metallocluster formation [1].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 149371-08-4

References:

1.	Zheng, L.M., White, R.H., Cash, V.L., Jack, R.F. and Dean, D.R. Cysteine desulfurase activity indicates a role for NIFS in metallocluster biosynthesis. Proc. Natl. Acad. Sci. USA 90 (1993) 2754–2758. [DOI] [PMID: 8464885]
2.	Mihara, H. and Esaki, N. Bacterial cysteine desulfurases: Their function and mechanisms. Appl. Microbiol. Biotechnol. 60 (2002) 12–23. [DOI] [PMID: 12382038]
3.	Frazzon, J. and Dean, D.R. Formation of iron-sulfur clusters in bacteria: An emerging field in bioinorganic chemistry. Curr. Opin. Chem. Biol. 7 (2003) 166–173. [DOI] [PMID: 12714048]

[EC 2.8.1.7 created 2003, modified 2011]

2.8.1.9

Accepted name:

molybdenum cofactor sulfurtransferase

Reaction:

molybdenum cofactor + L-cysteine + reduced acceptor + 2 H⁺ = thio-molybdenum cofactor + L-alanine + H₂O + oxidized acceptor

For diagram of MoCo biosynthesis, click here

Glossary:

Other name(s):

molybdenum cofactor sulfurase; ABA3; HMCS; MoCo sulfurase; MoCo sulfurtransferase

Systematic name:

L-cysteine:molybdenum cofactor sulfurtransferase

Comments:

Contains pyridoxal phosphate. Replaces the equatorial oxo ligand of the molybdenum by sulfur via an enzyme-bound persulfide. The reaction occurs in prokaryotes and eukaryotes but MoCo sulfurtransferases are only found in eukaryotes. In prokaryotes the reaction is catalysed by two enzymes: cysteine desulfurase (EC 2.8.1.7), which is homologous to the N-terminus of eukaryotic MoCo sulfurtransferases, and a molybdo-enzyme specific chaperone which binds the MoCo and acts as an adapter protein.

Links to other databases:

References:

1.	Bittner, F., Oreb, M. and Mendel, R.R. ABA3 is a molybdenum cofactor sulfurase required for activation of aldehyde oxidase and xanthine dehydrogenase in Arabidopsis thaliana. J. Biol. Chem. 276 (2001) 40381–40384. [DOI] [PMID: 11553608]
2.	Heidenreich, T., Wollers, S., Mendel, R.R. and Bittner, F. Characterization of the NifS-like domain of ABA3 from Arabidopsis thaliana provides insight into the mechanism of molybdenum cofactor sulfuration. J. Biol. Chem. 280 (2005) 4213–4218. [DOI] [PMID: 15561708]
3.	Wollers, S., Heidenreich, T., Zarepour, M., Zachmann, D., Kraft, C., Zhao, Y., Mendel, R.R. and Bittner, F. Binding of sulfurated molybdenum cofactor to the C-terminal domain of ABA3 from Arabidopsis thaliana provides insight into the mechanism of molybdenum cofactor sulfuration. J. Biol. Chem. 283 (2008) 9642–9650. [DOI] [PMID: 18258600]

[EC 2.8.1.9 created 2011, modified 2015]

2.8.1.10

Accepted name:

thiazole synthase

Reaction:

1-deoxy-D-xylulose 5-phosphate + 2-iminoacetate + thiocarboxy-[sulfur-carrier protein ThiS] = 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + [sulfur-carrier protein ThiS] + 2 H₂O

For diagram of thiamine diphosphate biosynthesis, click here

Glossary:

cThz*-P = 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate

Other name(s):

thiG (gene name)

Systematic name:

1-deoxy-D-xylulose 5-phosphate:thiol sulfurtransferase

Comments:

H₂S can provide the sulfur in vitro. Part of the pathway for thiamine biosynthesis.

Links to other databases:

References:

1.	Park, J.H., Dorrestein, P.C., Zhai, H., Kinsland, C., McLafferty, F.W. and Begley, T.P. Biosynthesis of the thiazole moiety of thiamin pyrophosphate (vitamin B₁). Biochemistry 42 (2003) 12430–12438. [DOI] [PMID: 14567704]
2.	Dorrestein, P.C., Zhai, H., McLafferty, F.W. and Begley, T.P. The biosynthesis of the thiazole phosphate moiety of thiamin: the sulfur transfer mediated by the sulfur carrier protein ThiS. Chem. Biol. 11 (2004) 1373–1381. [DOI] [PMID: 15489164]
3.	Dorrestein, P.C., Zhai, H., Taylor, S.V., McLafferty, F.W. and Begley, T.P. The biosynthesis of the thiazole phosphate moiety of thiamin (vitamin B₁): the early steps catalyzed by thiazole synthase. J. Am. Chem. Soc. 126 (2004) 3091–3096. [DOI] [PMID: 15012138]
4.	Settembre, E.C., Dorrestein, P.C., Zhai, H., Chatterjee, A., McLafferty, F.W., Begley, T.P. and Ealick, S.E. Thiamin biosynthesis in Bacillus subtilis: structure of the thiazole synthase/sulfur carrier protein complex. Biochemistry 43 (2004) 11647–11657. [DOI] [PMID: 15362849]
5.	Hazra, A., Chatterjee, A. and Begley, T.P. Biosynthesis of the thiamin thiazole in Bacillus subtilis: identification of the product of the thiazole synthase-catalyzed reaction. J. Am. Chem. Soc. 131 (2009) 3225–3229. [DOI] [PMID: 19216519]
6.	Hazra, A.B., Han, Y., Chatterjee, A., Zhang, Y., Lai, R.Y., Ealick, S.E. and Begley, T.P. A missing enzyme in thiamin thiazole biosynthesis: identification of TenI as a thiazole tautomerase. J. Am. Chem. Soc. 133 (2011) 9311–9319. [DOI] [PMID: 21534620]

[EC 2.8.1.10 created 2011, modified 2016]

2.8.1.11

Accepted name:

molybdopterin synthase sulfurtransferase

Reaction:

[molybdopterin-synthase sulfur-carrier protein]-Gly-Gly-AMP + [cysteine desulfurase]-S-sulfanyl-L-cysteine + reduced acceptor = AMP + [molybdopterin-synthase sulfur-carrier protein]-Gly-NH-CH₂-C(O)SH + [cysteine desulfurase]-L-cysteine + oxidized acceptor

For diagram of MoCo biosynthesis, click here

Other name(s):

adenylyltransferase and sulfurtransferase MOCS3; Cnx5 (gene name); molybdopterin synthase sulfurylase

Systematic name:

[cysteine desulfurase]-S-sulfanyl-L-cysteine:[molybdopterin-synthase sulfur-carrier protein]-Gly-Gly sulfurtransferase

Comments:

The enzyme transfers sulfur to form a thiocarboxylate moiety on the C-terminal glycine of the small subunit of EC 2.8.1.12, molybdopterin synthase. In the human, the reaction is catalysed by the rhodanese-like C-terminal domain (cf. EC 2.8.1.1) of the MOCS3 protein, a bifunctional protein that also contains EC 2.7.7.80, molybdopterin-synthase adenylyltransferase, at the N-terminal domain.

Links to other databases:

References:

1.	Matthies, A., Nimtz, M. and Leimkuhler, S. Molybdenum cofactor biosynthesis in humans: identification of a persulfide group in the rhodanese-like domain of MOCS3 by mass spectrometry. Biochemistry 44 (2005) 7912–7920. [DOI] [PMID: 15910006]
2.	Leimkuhler, S. and Rajagopalan, K.V. A sulfurtransferase is required in the transfer of cysteine sulfur in the in vitro synthesis of molybdopterin from precursor Z in Escherichia coli. J. Biol. Chem. 276 (2001) 22024–22031. [DOI] [PMID: 11290749]
3.	Hanzelmann, P., Dahl, J.U., Kuper, J., Urban, A., Muller-Theissen, U., Leimkuhler, S. and Schindelin, H. Crystal structure of YnjE from Escherichia coli, a sulfurtransferase with three rhodanese domains. Protein Sci. 18 (2009) 2480–2491. [DOI] [PMID: 19798741]
4.	Dahl, J.U., Urban, A., Bolte, A., Sriyabhaya, P., Donahue, J.L., Nimtz, M., Larson, T.J. and Leimkuhler, S. The identification of a novel protein involved in molybdenum cofactor biosynthesis in Escherichia coli. J. Biol. Chem. 286 (2011) 35801–35812. [DOI] [PMID: 21856748]

[EC 2.8.1.11 created 2011, modified 2016]

2.8.1.12

Accepted name:

molybdopterin synthase

Reaction:

cyclic pyranopterin phosphate + 2 [molybdopterin-synthase sulfur-carrier protein]-Gly-NH-CH₂-C(O)SH + H₂O = molybdopterin + 2 molybdopterin-synthase sulfur-carrier protein

For diagram of MoCo biosynthesis, click here

Glossary:

molybdopterin = H2Dtpp-mP = {[(5aR,8R,9aR)-2-amino-4-oxo-6,7-bis(sulfanyl-κS)-1,5,5a,8,9a,10-hexahydro-4H-pyrano[3,2-g]pteridin-8-yl]methyl dihydrogenato(2^-) phosphate}(dioxo)molybdate(2^-)
cyclic pyranopterin phosphate = cPMP = precursor Z = 8-amino-2,12,12-trihydroxy-4a,5a,6,9,11,11a,12,12a-octahydro[1,3,2]dioxaphosphinino[4′,5′:5,6]pyrano[3,2-g]pteridin-10(4H)-one 2-oxide = 8-amino-2,12,12-trihydroxy-4,4a,5a,6,9,10,11,11a,12,12a-decahydro-[1,3,2]dioxaphosphinino[4′,5′:5,6]pyrano[3,2-g]pteridine 2-oxide

Other name(s):

MPT synthase

Systematic name:

thiocarboxylated molybdopterin synthase:cyclic pyranopterin phosphate sulfurtransferase

Comments:

Catalyses the synthesis of molybdopterin from cyclic pyranopterin monophosphate. Two sulfur atoms are transferred to cyclic pyranopterin monophosphate in order to form the characteristic ene-dithiol group found in the molybdenum cofactor. Molybdopterin synthase consists of two large subunits forming a central dimer and two small subunits (molybdopterin-synthase sulfur-carrier proteins) that are thiocarboxylated at the C-terminus by EC 2.8.1.11, molybdopterin synthase sulfurtransferase. The reaction occurs in prokaryotes and eukaryotes.

Links to other databases:

References:

1.	Daniels, J.N., Wuebbens, M.M., Rajagopalan, K.V. and Schindelin, H. Crystal structure of a molybdopterin synthase-precursor Z complex: insight into its sulfur transfer mechanism and its role in molybdenum cofactor deficiency. Biochemistry 47 (2008) 615–626. [DOI] [PMID: 18092812]
2.	Wuebbens, M.M. and Rajagopalan, K.V. Mechanistic and mutational studies of Escherichia coli molybdopterin synthase clarify the final step of molybdopterin biosynthesis. J. Biol. Chem. 278 (2003) 14523–14532. [DOI] [PMID: 12571226]

[EC 2.8.1.12 created 2011]

*EC

2.8.4.1

Accepted name:

coenzyme-B sulfoethylthiotransferase

Reaction:

methyl-CoM + CoB = CoM-S-S-CoB + methane

For diagram of methane biosynthesis, click here

Glossary:

CoB = coenzyme B = N-(7-sulfanylheptanoyl)threonine = N-(7-mercaptoheptanoyl)threonine 3-O-phosphate (deprecated)
CoM = coenzyme M = 2-sulfanylethane-1-sulfonate = 2-mercaptoethanesulfonate (deprecated)

Other name(s):

methyl-CoM reductase; methyl coenzyme M reductase

Systematic name:

methyl-CoM:CoB S-(2-sulfoethyl)thiotransferase

Comments:

This enzyme catalyses the final step in methanogenesis, the biological production of methane. This important anaerobic process is carried out only by methanogenic archaea. The enzyme can also function in reverse, for anaerobic oxidation of methane.The enzyme requires the hydroporphinoid nickel complex coenzyme F₄₃₀. Highly specific for coenzyme B with a heptanoyl chain; ethyl CoM and difluoromethyl CoM are poor substrates. The sulfide sulfur can be replaced by selenium but not by oxygen.

Links to other databases:

References:

1.	Bobik, T.A., Olson, K.D., Noll, K.M. and Wolfe, R.S. Evidence that the heterodisulfide of coenzyme-M and 7-mercaptanoylthreonine phosphate is a product of the methylreductase reaction in Methanobacterium. Biochem. Biophys. Res. Commun. 149 (1987) 455–460. [DOI] [PMID: 3122735]
2.	Ellermann, J., Hedderich, R., Boecher, R. and Thauer, R.K. The final step in methane formation: investigations with highly purified methyl coenzyme M reductase component C from Methanobacterium thermoautotrophicum (strain Marburg). Eur. J. Biochem. 184 (1988) 63–68.
3.	Ermler, U., Grabarse, W., Shima, S., Goubeaud, M. and Thauer, R.K. Crystal structure of methyl coenzyme M reductase: The key enzyme of biological methane formation. Science 278 (1997) 1457–1462. [DOI] [PMID: 9367957]
4.	Signor, L., Knuppe, C., Hug, R., Schweizer, B., Pfaltz, A. and Jaun, B. Methane formation by reaction of a methyl thioether with a photo-excited nickel thiolate — a process mimicking methanogenesis in Archaea. Chemistry 6 (2000) 3508–3516. [PMID: 11072815]
5.	Scheller, S., Goenrich, M., Boecher, R., Thauer, R.K. and Jaun, B. The key nickel enzyme of methanogenesis catalyses the anaerobic oxidation of methane. Nature 465 (2010) 606–608. [DOI] [PMID: 20520712]

[EC 2.8.4.1 created 2001, modified 2011]

3.1.1.21

Deleted entry:

retinyl-palmitate esterase. Now known to be catalysed by EC 3.1.1.1, carboxylesterase and EC 3.1.1.3, triacylglycerol lipase.

[EC 3.1.1.21 created 1972, deleted 2011]

*EC

3.1.1.64

Accepted name:

retinoid isomerohydrolase

Reaction:

an all-trans-retinyl ester + H₂O = 11-cis-retinol + a fatty acid

For diagram of retinal and derivatives biosynthesis, click here

Other name(s):

all-trans-retinyl-palmitate hydrolase (ambiguous); retinol isomerase (ambiguous); all-trans-retinol isomerase:hydrolase (ambiguous); all-trans-retinylester 11-cis isomerohydrolase; RPE65 (gene name)

Systematic name:

all-trans-retinyl ester acylhydrolase, 11-cis retinol-forming

Comments:

This enzyme, which operates in the retinal pigment epithelium (RPE), catalyses the cleavage and isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol, a key step in the regeneration of the visual chromophore in the vertebrate visual cycle [4]. Interaction of the enzyme with the membrane is critical for its enzymic activity [6].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 106389-24-6

References:

1.	Blaner, W.S., Das, S.R., Gouras, P. and Flood, M.T. Hydrolysis of 11-cis- and all-trans-retinyl palmitate by homogenates of human retinal epithelial cells. J. Biol. Chem. 262 (1987) 53–58. [PMID: 3793734]
2.	Bernstein, P.S., Law, W.C. and Rando, R.R. Isomerization of all-trans-retinoids to 11-cis-retinoids in vitro. Proc. Natl. Acad. Sci. USA 84 (1987) 1849–1853. [DOI] [PMID: 3494246]
3.	Bridges, C.D. and Alvarez, R.A. The visual cycle operates via an isomerase acting on all-trans retinol in the pigment epithelium. Science 236 (1987) 1678–1680. [DOI] [PMID: 3603006]
4.	Moiseyev, G., Chen, Y., Takahashi, Y., Wu, B.X. and Ma, J.X. RPE65 is the isomerohydrolase in the retinoid visual cycle. Proc. Natl. Acad. Sci. USA 102 (2005) 12413–12418. [DOI] [PMID: 16116091]
5.	Nikolaeva, O., Takahashi, Y., Moiseyev, G. and Ma, J.X. Purified RPE65 shows isomerohydrolase activity after reassociation with a phospholipid membrane. FEBS J. 276 (2009) 3020–3030. [DOI] [PMID: 19490105]
6.	Golczak, M., Kiser, P.D., Lodowski, D.T., Maeda, A. and Palczewski, K. Importance of membrane structural integrity for RPE65 retinoid isomerization activity. J. Biol. Chem. 285 (2010) 9667–9682. [DOI] [PMID: 20100834]

[EC 3.1.1.64 created 1989 (EC 5.2.1.7 created 1989, incorporated 2011), modified 2011]

3.1.1.89

Accepted name:

protein phosphatase methylesterase-1

Reaction:

[phosphatase 2A protein]-leucine methyl ester + H₂O = [phosphatase 2A protein]-leucine + methanol

Other name(s):

PME-1; PPME1

Systematic name:

[phosphatase 2A protein]-leucine ester acylhydrolase

Comments:

A key regulator of protein phosphatase 2A. The methyl ester is formed by EC 2.1.1.233 (leucine carboxy methyltransferase-1). Occurs mainly in the nucleus.

Links to other databases:

References:

1.	Ogris, E., Du, X., Nelson, K.C., Mak, E.K., Yu, X.X., Lane, W.S. and Pallas, D.C. A protein phosphatase methylesterase (PME-1) is one of several novel proteins stably associating with two inactive mutants of protein phosphatase 2A. J. Biol. Chem. 274 (1999) 14382–14391. [DOI] [PMID: 10318862]
2.	Xing, Y., Li, Z., Chen, Y., Stock, J.B., Jeffrey, P.D. and Shi, Y. Structural mechanism of demethylation and inactivation of protein phosphatase 2A. Cell 133 (2008) 154–163. [DOI] [PMID: 18394995]

[EC 3.1.1.89 created 2011]

3.1.1.90

Accepted name:

all-trans-retinyl ester 13-cis isomerohydrolase

Reaction:

an all-trans-retinyl ester + H₂O = 13-cis-retinol + a fatty acid

For diagram of retinal and derivatives biosynthesis, click here

Systematic name:

all-trans-retinyl ester acylhydrolase, 13-cis-retinol-forming

Comments:

All-trans-retinyl esters, which are a storage form of vitamin A, are generated by the activity of EC 2.3.1.135, phosphatidylcholine—retinol O-acyltransferase (LRAT). They can be hydrolysed to 11-cis-retinol by EC 3.1.1.64, retinoid isomerohydrolase (RPE65), or to 13-cis-retinol by this enzyme.

Links to other databases:

References:

1.	Takahashi, Y., Moiseyev, G., Chen, Y., Farjo, K., Nikolaeva, O. and Ma, J.X. An enzymatic mechanism for generating the precursor of endogenous 13-cis retinoic acid in the brain. FEBS J. 278 (2011) 973–987. [DOI] [PMID: 21235714]

[EC 3.1.1.90 created 2011]

3.1.3.86

Accepted name:

phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase

Reaction:

1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate + H₂O = 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + phosphate

For diagram of 1-phosphatidyl-myo-inositol metabolism, click here

Glossary:

1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate = PtdIns(3,4)P₂
1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate = PtdIns(3,4,5)P₃
1-phosphatidyl-1D-myo-inositol 1,3,4,5-trisphosphate = PtdIns(1,3,4,5)P₄

Other name(s):

SHIP1; SHIP2; SHIP; p150Ship

Systematic name:

1-phosphatidyl-1D-myo-inositol-3,4,5-trisphosphate 5-phosphohydrolase

Comments:

This enzyme hydrolyses 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate (PtdIns(3,4,5)P₃) to produce PtdIns(3,4)P₂, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. The enzyme also shows activity toward (PtdIns(1,3,4,5)P₄) [5]. The enzyme is involved in several signal transduction pathways in the immune system leading to an adverse range of effects.

Links to other databases:

References:

1.	Lioubin, M.N., Algate, P.A., Tsai, S., Carlberg, K., Aebersold, A. and Rohrschneider, L.R. p150Ship, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity. Genes Dev. 10 (1996) 1084–1095. [DOI] [PMID: 8654924]
2.	Damen, J.E., Liu, L., Rosten, P., Humphries, R.K., Jefferson, A.B., Majerus, P.W. and Krystal, G. The 145-kDa protein induced to associate with Shc by multiple cytokines is an inositol tetraphosphate and phosphatidylinositol 3,4,5-triphosphate 5-phosphatase. Proc. Natl. Acad. Sci. USA 93 (1996) 1689–1693. [DOI] [PMID: 8643691]
3.	Giuriato, S., Payrastre, B., Drayer, A.L., Plantavid, M., Woscholski, R., Parker, P., Erneux, C. and Chap, H. Tyrosine phosphorylation and relocation of SHIP are integrin-mediated in thrombin-stimulated human blood platelets. J. Biol. Chem. 272 (1997) 26857–26863. [DOI] [PMID: 9341117]
4.	Drayer, A.L., Pesesse, X., De Smedt, F., Woscholski, R., Parker, P. and Erneux, C. Cloning and expression of a human placenta inositol 1,3,4,5-tetrakisphosphate and phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase. Biochem. Biophys. Res. Commun. 225 (1996) 243–249. [DOI] [PMID: 8769125]
5.	Pesesse, X., Moreau, C., Drayer, A.L., Woscholski, R., Parker, P. and Erneux, C. The SH₂ domain containing inositol 5-phosphatase SHIP2 displays phosphatidylinositol 3,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate 5-phosphatase activity. FEBS Lett. 437 (1998) 301–303. [DOI] [PMID: 9824312]

[EC 3.1.3.86 created 2011]

3.1.4.54

Accepted name:

N-acetylphosphatidylethanolamine-hydrolysing phospholipase D

Reaction:

N-acylphosphatidylethanolamine + H₂O = N-acylethanolamine + a 1,2-diacylglycerol 3-phosphate

Other name(s):

NAPE-PLD; anandamide-generating phospholipase D; N-acyl phosphatidylethanolamine phospholipase D; NAPE-hydrolyzing phospholipase D

Systematic name:

N-acetylphosphatidylethanolamine phosphatidohydrolase

Comments:

This enzyme is involved in the biosynthesis of anandamide. It does not hydrolyse phosphatidylcholine and phosphatidylethanolamine [1]. No transphosphatidation [1]. The enzyme contains Zn²⁺ and is activated by Mg²⁺ or Ca²⁺ [2].

Links to other databases:

References:

1.	Okamoto, Y., Morishita, J., Tsuboi, K., Tonai, T. and Ueda, N. Molecular characterization of a phospholipase D generating anandamide and its congeners. J. Biol. Chem. 279 (2004) 5298–5305. [DOI] [PMID: 14634025]
2.	Wang, J., Okamoto, Y., Morishita, J., Tsuboi, K., Miyatake, A. and Ueda, N. Functional analysis of the purified anandamide-generating phospholipase D as a member of the metallo-β-lactamase family. J. Biol. Chem. 281 (2006) 12325–12335. [DOI] [PMID: 16527816]

[EC 3.1.4.54 created 2011]

3.1.7.8

Transferred entry:

tuberculosinol synthase. Now known to be partial activity of EC 2.5.1.153, adenosine tuberculosinyltransferase.

[EC 3.1.7.8 created 2011, deleted 2020]

3.1.7.9

Transferred entry:

isotuberculosinol synthase. Now known to be partial activity of EC 2.5.1.153, adenosine tuberculosinyltransferase.

[EC 3.1.7.9 created 2011, deleted 2020]

*EC

3.2.1.32

Accepted name:

endo-1,3-β-xylanase

Reaction:

Random endohydrolysis of (1→3)-β-D-glycosidic linkages in (1→3)-β-D-xylans

Other name(s):

xylanase (ambiguous); endo-1,3-β-xylosidase (misleading); 1,3-β-xylanase; 1,3-xylanase; β-1,3-xylanase; endo-β-1,3-xylanase; 1,3-β-D-xylan xylanohydrolase; xylan endo-1,3-β-xylosidase

Systematic name:

3-β-D-xylan xylanohydrolase

Comments:

This enzyme is found mostly in marine bacteria, which break down the β(1,3)-xylan found in the cell wall of some green and red algae. The enzyme produces mainly xylobiose, xylotriose and xylotetraose.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9025-55-2

References:

1.	Chen, W.P., Matsuo, M. and Tsuneo, Y. Purification and some properties of β-1,3-xylanase from Aspergillus terreus A-07. Agric. Biol. Chem. 50 (1986) 1183–1194.
2.	Aoki, T., Araki, T. and Kitamikado, M. Purification and characterization of an endo-β-1,3-xylanase from Vibrio species. Nippon Suisan Gakkaishi 54 (1988) 277–281.
3.	Araki, T., Tani, S., Maeda, K., Hashikawa, S., Nakagawa, H. and Morishita, T. Purification and characterization of β-1,3-xylanase from a marine bacterium, Vibrio sp. XY-214. Biosci. Biotechnol. Biochem. 63 (1999) 2017–2019. [PMID: 10635569]
4.	Araki, T., Inoue, N. and Morishita, T. Purification and characterization of β-1,3-xylanase from a marine bacterium, Alcaligenes sp. XY-234. J. Gen. Appl. Microbiol. 44 (1998) 269–274. [PMID: 12501421]
5.	Okazaki, F., Shiraki, K., Tamaru, Y., Araki, T. and Takagi, M. The first thermodynamic characterization of β-1,3-xylanase from a marine bacterium. Protein J. 24 (2005) 413–421. [DOI] [PMID: 16328734]

[EC 3.2.1.32 created 1965, modified 2011]

*EC

3.2.1.47

Deleted entry:

galactosylgalactosylglucosylceramidase. Now known to be catalyzed by EC 3.2.1.22, α-galactosidase.

[EC 3.2.1.47 created 1972, modified 2011, deleted 2021]

*EC

3.2.1.91

Accepted name:

cellulose 1,4-β-cellobiosidase (non-reducing end)

Reaction:

Hydrolysis of (1→4)-β-D-glucosidic linkages in cellulose and cellotetraose, releasing cellobiose from the non-reducing ends of the chains

Other name(s):

exo-cellobiohydrolase; β-1,4-glucan cellobiohydrolase; β-1,4-glucan cellobiosylhydrolase; 1,4-β-glucan cellobiosidase; exoglucanase; avicelase; CBH 1; C₁ cellulase; cellobiohydrolase I; cellobiohydrolase; exo-β-1,4-glucan cellobiohydrolase; 1,4-β-D-glucan cellobiohydrolase; cellobiosidase

Systematic name:

4-β-D-glucan cellobiohydrolase (non-reducing end)

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 37329-65-0

References:

1.	Berghem, L.E.R. and Pettersson, L.G. The mechanism of enzymatic cellulose degradation. Purification of a cellulolytic enzyme from Trichoderma viride active on highly ordered cellulose. Eur. J. Biochem. 37 (1973) 21–30. [DOI] [PMID: 4738092]
2.	Eriksson, K.E. and Pettersson, B. Extracellular enzyme system utilized by the fungus Sporotrichum pulverulentum (Chrysosporium lignorum) for the breakdown of cellulose. 3. Purification and physico-chemical characterization of an exo-1,4-β-glucanase. Eur. J. Biochem. 51 (1975) 213–218. [DOI] [PMID: 235428]
3.	Halliwell, G., Griffin, M. and Vincent, R. The role of component C₁ in cellulolytic systems. Biochem. J. 127 (1972) 43P. [PMID: 5076675]

[EC 3.2.1.91 created 1976, modified 2011]

*EC

3.2.1.99

Accepted name:

arabinan endo-1,5-α-L-arabinanase

Reaction:

Endohydrolysis of (1→5)-α-arabinofuranosidic linkages in (1→5)-arabinans

Other name(s):

endo-1,5-α-L-arabinanase; endo-α-1,5-arabanase; endo-arabanase; 1,5-α-L-arabinan 1,5-α-L-arabinanohydrolase; arabinan endo-1,5-α-L-arabinosidase (misleading)

Systematic name:

5-α-L-arabinan 5-α-L-arabinanohydrolase

Comments:

Acts best on linear 1,5-α-L-arabinan. Also acts on branched arabinan, but more slowly.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 75432-96-1

References:

1.	Kaji, A. and Saheki, T. Endo-arabinanase from Bacillus subtilis F-11. Biochim. Biophys. Acta 410 (1975) 354–360. [DOI] [PMID: 1096]
2.	Weinstein, L. and Albersheim, P. Structure of plant cell walls. IX. Purification and partial characterization of a wall-degrading endo-arabinase and an arabinosidase from Bacillus subtilis. Plant Physiol. 63 (1979) 425–432. [PMID: 16660741]
3.	Flipphi, M.J., Panneman, H., van der Veen, P., Visser, J. and de Graaff, L.H. Molecular cloning, expression and structure of the endo-1,5-α-L-arabinase gene of Aspergillus niger. Appl. Microbiol. Biotechnol. 40 (1993) 318–326. [PMID: 7764386]
4.	Leal, T.F. and de Sa-Nogueira, I. Purification, characterization and functional analysis of an endo-arabinanase (AbnA) from Bacillus subtilis. FEMS Microbiol. Lett. 241 (2004) 41–48. [DOI] [PMID: 15556708]

[EC 3.2.1.99 created 1981, modified 2011]

*EC

3.2.1.155

Accepted name:

xyloglucan-specific endo-processive β-1,4-glucanase

Reaction:

Hydrolysis of (1→4)-D-glucosidic linkages in xyloglucans so as to successively remove oligosaccharides from the newly-formed chain end after endo-initiation on a polymer molecule

Other name(s):

Cel74A; [(1→6)-α-D-xylo]-(1→4)-β-D-glucan exo-glucohydrolase (ambiguous); xyloglucan-specific exo-β-1,4-glucanase (ambiguous)

Systematic name:

[(1→6)-α-D-xylo]-(1→4)-β-D-glucan endo-processive glucohydrolase

Comments:

The enzyme removes branched oligosaccharides, containing preferentially four glucoside residues in the main chain, from xyloglucan molecules in a processive manner after the initial endo-type attack on a polysaccharide [1-5]. Hydrolysis occurs at either the unsubstituted D-glucopyranose residue in the main backbone and/or the D-glucopyranose residue bearing a xylosyl group [1-5]. The enzyme does not display activity, or shows very low activity, towards other β-D-glucans [1,2,4,5].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 1000598-79-7

References:

1.	Grishutin, S.G., Gusakov, A.V., Markov, A.V., Ustinov, B.B., Semenova, M.V. and Sinitsyn, A.P. Specific xyloglucanases as a new class of polysaccharide-degrading enzymes. Biochim. Biophys. Acta 1674 (2004) 268–281. [DOI] [PMID: 15541296]
2.	Ichinose, H., Araki, Y., Michikawa, M., Harazono, K., Yaoi, K., Karita, S. and Kaneko, S. Characterization of an endo-processive-type xyloglucanase having a β-1,4-glucan-binding module and an endo-type xyloglucanase from Streptomyces avermitilis. Appl. Environ. Microbiol. 78 (2012) 7939–7945. [PMID: 22941084]
3.	Matsuzawa, T., Saito, Y. and Yaoi, K. Key amino acid residues for the endo-processive activity of GH74 xyloglucanase. FEBS Lett. 588 (2014) 1731–1738. [PMID: 24657616]
4.	Arnal, G., Stogios, P.J., Asohan, J., Skarina, T., Savchenko, A. and Brumer, H. Structural enzymology reveals the molecular basis of substrate regiospecificity and processivity of an exemplar bacterial glycoside hydrolase family 74 endo-xyloglucanase. Biochem. J. 475 (2018) 3963–3978. [PMID: 30463871]
5.	Arnal, G., Stogios, P.J., Asohan, J., Attia, M.A., Skarina, T., Viborg, A.H., Henrissat, B., Savchenko, A. and Brumer, H. Substrate specificity, regiospecificity, and processivity in glycoside hydrolase family 74. J. Biol. Chem. 294 (2019) 13233–13247. [PMID: 31324716]
6.	Gusakov, A.V. Additional sequence and structural characterization of an endo-processive GH74 xyloglucanase from Myceliophthora thermophila and the revision of the EC 3.2.1.155 entry. Biochim. Biophys. Acta. 1864:129511 (2020). [PMID: 31911243]

[EC 3.2.1.155 created 2005, withdrawn at public-review stage, modified and reinstated 2006, modified 2020]

3.2.1.176

Accepted name:

cellulose 1,4-β-cellobiosidase (reducing end)

Reaction:

Hydrolysis of (1→4)-β-D-glucosidic linkages in cellulose and similar substrates, releasing cellobiose from the reducing ends of the chains.

Other name(s):

CelS; CelSS; endoglucanase SS; cellulase SS; cellobiohydrolase CelS; Cel48A

Systematic name:

4-β-D-glucan cellobiohydrolase (reducing end)

Comments:

Some exocellulases, most of which belong to the glycoside hydrolase family 48 (GH48, formerly known as cellulase family L), act at the reducing ends of cellulose and similar substrates. The CelS enzyme from Clostridium thermocellum is the most abundant subunit of the cellulosome formed by the organism. It liberates cellobiose units from the reducing end by hydrolysis of the glycosidic bond, employing an inverting reaction mechanism [2]. Different from EC 3.2.1.91, which attacks cellulose from the non-reducing end.

Links to other databases:

References:

1.	Barr, B.K., Hsieh, Y.L., Ganem, B. and Wilson, D.B. Identification of two functionally different classes of exocellulases. Biochemistry 35 (1996) 586–592. [DOI] [PMID: 8555231]
2.	Saharay, M., Guo, H. and Smith, J.C. Catalytic mechanism of cellulose degradation by a cellobiohydrolase, CelS. PLoS One 5:e1294 (2010). [DOI] [PMID: 20967294]

[EC 3.2.1.176 created 2011]

3.2.1.177

Accepted name:

α-D-xyloside xylohydrolase

Reaction:

Hydrolysis of terminal, non-reducing α-D-xylose residues with release of α-D-xylose.

Other name(s):

α-xylosidase

Systematic name:

α-D-xyloside xylohydrolase

Comments:

The enzyme catalyses hydrolysis of a terminal, unsubstituted xyloside at the extreme reducing end of a xylogluco-oligosaccharide. Representative α-xylosidases from glycoside hydrolase family 31 utilize a two-step (double-displacement) mechanism involving a covalent glycosyl-enzyme intermediate, and retain the anomeric configuration of the product.

Links to other databases:

References:

1.	Moracci, M., Cobucci Ponzano, B., Trincone, A., Fusco, S., De Rosa, M., van Der Oost, J., Sensen, C.W., Charlebois, R.L. and Rossi, M. Identification and molecular characterization of the first α -xylosidase from an archaeon. J. Biol. Chem. 275 (2000) 22082–22089. [DOI] [PMID: 10801892]
2.	Sampedro, J., Sieiro, C., Revilla, G., Gonzalez-Villa, T. and Zarra, I. Cloning and expression pattern of a gene encoding an α-xylosidase active against xyloglucan oligosaccharides from Arabidopsis. Plant Physiol. 126 (2001) 910–920. [PMID: 11402218]
3.	Crombie, H.J., Chengappa, S., Jarman, C., Sidebottom, C. and Reid, J.S. Molecular characterisation of a xyloglucan oligosaccharide-acting α-D-xylosidase from nasturtium (Tropaeolum majus L.) cotyledons that resembles plant ’apoplastic’ α-D-glucosidases. Planta 214 (2002) 406–413. [PMID: 11859845]
4.	Lovering, A.L., Lee, S.S., Kim, Y.W., Withers, S.G. and Strynadka, N.C. Mechanistic and structural analysis of a family 31 α-glycosidase and its glycosyl-enzyme intermediate. J. Biol. Chem. 280 (2005) 2105–2115. [DOI] [PMID: 15501829]
5.	Iglesias, N., Abelenda, J.A., Rodino, M., Sampedro, J., Revilla, G. and Zarra, I. Apoplastic glycosidases active against xyloglucan oligosaccharides of Arabidopsis thaliana. Plant Cell Physiol. 47 (2006) 55–63. [DOI] [PMID: 16267099]
6.	Okuyama, M., Kaneko, A., Mori, H., Chiba, S. and Kimura, A. Structural elements to convert Escherichia coli α-xylosidase (YicI) into α-glucosidase. FEBS Lett. 580 (2006) 2707–2711. [DOI] [PMID: 16631751]
7.	Larsbrink, J., Izumi, A., Ibatullin, F., Nakhai, A., Gilbert, H.J., Davies, G.J. and Brumer, H. Structural and enzymatic characterisation of a glycoside hydrolase family 31 α-xylosidase from Cellvibrio japonicus involved in xyloglucan saccharification. Biochem. J. 436 (2011) 567–580. [DOI] [PMID: 21426303]

[EC 3.2.1.177 created 2011]

3.2.1.178

Accepted name:

β-porphyranase

Reaction:

Hydrolysis of β-D-galactopyranose-(1→4)-α-L-galactopyranose-6-sulfate linkages in porphyran

Other name(s):

porphyranase; PorA; PorB; endo-β-porphyranase

Systematic name:

porphyran β-D-galactopyranose-(1→4)-α-L-galactopyranose-6-sulfate 4-glycanohydrolase

Comments:

The backbone of porphyran consists largely (~70%) of (1→3)-linked β-D-galactopyranose followed by (1→4)-linked α-L-galactopyranose-6-sulfate [the other 30% are mostly agarobiose repeating units of (1→3)-linked β-D-galactopyranose followed by (1→4)-linked 3,6-anhydro-α-L-galactopyranose] [2]. This enzyme cleaves the (1→4) linkages between β-D-galactopyranose and α-L-galactopyranose-6-sulfate, forming mostly the disaccharide α-L-galactopyranose-6-sulfate-(1→3)-β-D-galactose, although some longer oligosaccharides of even number of residues are also observed. Since the enzyme is inactive on the non-sulfated agarose portion of the porphyran backbone, some agarose fragments are also included in the products [1]. Methylation of the D-galactose prevents the enzyme from Zobellia galactanivorans, but not that from Wenyingzhuangia fucanilytica, from binding at subsite -1 [2,3].

Links to other databases:

References:

1.	Hehemann, J.H., Correc, G., Barbeyron, T., Helbert, W., Czjzek, M. and Michel, G. Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature 464 (2010) 908–912. [DOI] [PMID: 20376150]
2.	Correc, G., Hehemann, J.H., Czjzek, M. and Helbert, W. Structural analysis of the degradation products of porphyran digested by Zobellia galactanivorans β-porphyranase A. Carbohydrate Polymers 83 (2011) 277–283.
3.	Zhang, Y., Chang, Y., Shen, J., Mei, X. and Xue, C. Characterization of a novel porphyranase accommodating methyl-galactoses at its subsites. J. Agr. Food Chem. 68 (2020) 7032–7039. [PMID: 32520542]

[EC 3.2.1.178 created 2011]

3.2.1.179

Accepted name:

gellan tetrasaccharide unsaturated glucuronosyl hydrolase

Reaction:

β-D-4-deoxy-Δ⁴-GlcAp-(1→4)-β-D-Glcp-(1→4)-α-L-Rhap-(1→3)-D-Glcp + H₂O = 5-dehydro-4-deoxy-D-glucuronate + β-D-Glcp-(1→4)-α-L-Rhap-(1→3)-D-Glcp

Glossary:

5-dehydro-4-deoxy-D-glucuronate = (4S,5R)-4,5-dihydroxy-2,6-dioxohexanoate
β-D-4-deoxy-Δ⁴-GlcAp-(1→3)-D-GalNAc = 3-(4-deoxy-β-D-gluc-4-enuronosyl)-N-acetyl-D-galactosamine = 3-(4-deoxy-α-L-threo-hex-4-enopyranosyluronic acid)-2-acetamido-2-deoxy-D-galactose

Other name(s):

UGL (ambiguous); unsaturated glucuronyl hydrolase (ambiguous); gellan tetrasaccharide unsaturated glucuronyl hydrolase

Systematic name:

β-D-4-deoxy-Δ⁴-GlcAp-(1→4)-β-D-Glcp-(1→4)-α-L-Rhap-(1→3)-D-Glcp β-D-4-deoxy-Δ⁴-GlcAp hydrolase

Comments:

The enzyme releases 4-deoxy-4(5)-unsaturated D-glucuronic acid from oligosaccharides produced by polysaccharide lyases, e.g. the tetrasaccharide β-D-4-deoxy-Δ⁴-GlcAp-(1→4)-β-D-Glcp-(1→4)-α-L-Rhap-(1→3)-D-Glcp produced by EC 4.2.2.25, gellan lyase. The enzyme can also hydrolyse unsaturated chondroitin and hyaluronate disaccharides (β-D-4-deoxy-Δ⁴-GlcAp-(1→3)-D-GalNAc, β-D-4-deoxy-Δ⁴-GlcAp-(1→3)-D-GalNAc6S, β-D-4-deoxy-Δ⁴-GlcAp2S-(1→3)-D-GalNAc, β-D-4-deoxy-Δ⁴-GlcAp-(1→3)-D-GlcNAc), preferring the unsulfated disaccharides to the sulfated disaccharides.

Links to other databases:

References:

1.	Itoh, T., Akao, S., Hashimoto, W., Mikami, B. and Murata, K. Crystal structure of unsaturated glucuronyl hydrolase, responsible for the degradation of glycosaminoglycan, from Bacillus sp. GL1 at 1.8 Å resolution. J. Biol. Chem. 279 (2004) 31804–31812. [DOI] [PMID: 15148314]
2.	Hashimoto, W., Kobayashi, E., Nankai, H., Sato, N., Miya, T., Kawai, S. and Murata, K. Unsaturated glucuronyl hydrolase of Bacillus sp. GL1: novel enzyme prerequisite for metabolism of unsaturated oligosaccharides produced by polysaccharide lyases. Arch. Biochem. Biophys. 368 (1999) 367–374. [DOI] [PMID: 10441389]
3.	Itoh, T., Hashimoto, W., Mikami, B. and Murata, K. Substrate recognition by unsaturated glucuronyl hydrolase from Bacillus sp. GL1. Biochem. Biophys. Res. Commun. 344 (2006) 253–262. [DOI] [PMID: 16630576]

[EC 3.2.1.179 created 2011, modified 2016]

3.2.1.180

Accepted name:

unsaturated chondroitin disaccharide hydrolase

Reaction:

β-D-4-deoxy-Δ⁴-GlcAp-(1→3)-β-D-GalNAc6S + H₂O = 5-dehydro-4-deoxy-D-glucuronate + N-acetyl-β-D-galactosamine-6-O-sulfate

Glossary:

5-dehydro-4-deoxy-D-glucuronate = (4S,5R)-4,5-dihydroxy-2,6-dioxohexanoate

Other name(s):

UGL (ambiguous); unsaturated glucuronyl hydrolase (ambiguous)

Systematic name:

β-D-4-deoxy-Δ⁴-GlcAp-(1→3)-β-D-GalNAc6S hydrolase

Comments:

The enzyme releases 4-deoxy-4,5-didehydro D-glucuronic acid or 4-deoxy-4,5-didehydro L-iduronic acid from chondroitin disaccharides, hyaluronan disaccharides and heparin disaccharides and cleaves both glycosidic (1→3) and (1→4) bonds. It prefers the sulfated disaccharides to the unsulfated disaccharides.

Links to other databases:

References:

1.	Maruyama, Y., Nakamichi, Y., Itoh, T., Mikami, B., Hashimoto, W. and Murata, K. Substrate specificity of streptococcal unsaturated glucuronyl hydrolases for sulfated glycosaminoglycan. J. Biol. Chem. 284 (2009) 18059–18069. [DOI] [PMID: 19416976]
2.	Nakamichi, Y., Maruyama, Y., Mikami, B., Hashimoto, W. and Murata, K. Structural determinants in streptococcal unsaturated glucuronyl hydrolase for recognition of glycosaminoglycan sulfate groups. J. Biol. Chem. 286 (2011) 6262–6271. [DOI] [PMID: 21147778]

[EC 3.2.1.180 created 2011]

3.4.11.26

Accepted name:

intermediate cleaving peptidase 55

Reaction:

The enzyme cleaves the Pro³⁶-Pro³⁷ bond of cysteine desulfurase (EC 2.8.1.7) removing three amino acid residues (Tyr-Ser-Pro) from the N-terminus after cleavage by mitochondrial processing peptidase.

Other name(s):

Icp55; mitochondrial intermediate cleaving peptidase 55 kDa

Comments:

Icp55 removes the destabilizing N-terminal amino acid residues that are left after cleavage by the mitochondrial processing peptidase, leading to the stabilisation of the substrate. The enzyme can remove single amino acids or a short peptide, as in the case of cysteine desulfurase (EC 2.8.1.7), where three amino acids are removed.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, MEROPS, PDB

References:

1.	Naamati, A., Regev-Rudzki, N., Galperin, S., Lill, R. and Pines, O. Dual targeting of Nfs1 and discovery of its novel processing enzyme, Icp55. J. Biol. Chem. 284 (2009) 30200–30208. [DOI] [PMID: 19720832]
2.	Vogtle, F.N., Wortelkamp, S., Zahedi, R.P., Becker, D., Leidhold, C., Gevaert, K., Kellermann, J., Voos, W., Sickmann, A., Pfanner, N. and Meisinger, C. Global analysis of the mitochondrial N-proteome identifies a processing peptidase critical for protein stability. Cell 139 (2009) 428–439. [DOI] [PMID: 19837041]

[EC 3.4.11.26 created 2011]

3.4.19.13

Accepted name:

glutathione γ-glutamate hydrolase

Reaction:

(1) glutathione + H₂O = L-cysteinylglycine + L-glutamate
(2) a glutathione-S-conjugate + H₂O = an (L-cysteinylglycine)-S-conjugate + L-glutamate

Other name(s):

glutathionase; γ-glutamyltranspeptidase (ambiguous); glutathione hydrolase; GGT (gene name); ECM38 (gene name)

Comments:

This is a bifunctional protein that also has the activity of EC 2.3.2.2, γ-glutamyltransferase. The enzyme binds its substrate by forming an initial γ-glutamyl-enzyme intermediate, releasing the L-cysteinylglycine part of the molecule. The enzyme then reacts with either a water molecule or a different acceptor substrate (usually an L-amino acid or a dipeptide) to form L-glutamate or a product containing a new γ-glutamyl isopeptide bond, respectively. The enzyme acts on glutathione, glutathione-S-conjugates, and, at a lower level, on other substrates with an N-terminal L-γ-glutamyl residue. It plays a crucial part in the glutathione-mediated xenobiotic detoxification pathway. The enzyme consists of two chains that are created by the proteolytic cleavage of a single precursor polypeptide.

Links to other databases:

References:

1.	Hanigan, M.H. and Ricketts, W.A. Extracellular glutathione is a source of cysteine for cells that express γ-glutamyl transpeptidase. Biochemistry 32 (1993) 6302–6306. [PMID: 8099811]
2.	Carter, B.Z., Wiseman, A.L., Orkiszewski, R., Ballard, K.D., Ou, C.N. and Lieberman, M.W. Metabolism of leukotriene C₄ in γ-glutamyl transpeptidase-deficient mice. J. Biol. Chem. 272 (1997) 12305–12310. [DOI] [PMID: 9139674]
3.	Suzuki, H. and Kumagai, H. Autocatalytic processing of γ-glutamyltranspeptidase. J. Biol. Chem. 277 (2002) 43536–43543. [DOI] [PMID: 12207027]
4.	Okada, T., Suzuki, H., Wada, K., Kumagai, H. and Fukuyama, K. Crystal structures of γ-glutamyltranspeptidase from Escherichia coli, a key enzyme in glutathione metabolism, and its reaction intermediate. Proc. Natl. Acad. Sci. USA 103 (2006) 6471–6476. [DOI] [PMID: 16618936]
5.	Boanca, G., Sand, A., Okada, T., Suzuki, H., Kumagai, H., Fukuyama, K. and Barycki, J.J. Autoprocessing of Helicobacter pylori γ-glutamyltranspeptidase leads to the formation of a threonine-threonine catalytic dyad. J. Biol. Chem. 282 (2007) 534–541. [DOI] [PMID: 17107958]
6.	Okada, T., Suzuki, H., Wada, K., Kumagai, H. and Fukuyama, K. Crystal structure of the γ-glutamyltranspeptidase precursor protein from Escherichia coli. Structural changes upon autocatalytic processing and implications for the maturation mechanism. J. Biol. Chem. 282 (2007) 2433–2439. [DOI] [PMID: 17135273]
7.	Grzam, A., Martin, M.N., Hell, R. and Meyer, A.J. γ-Glutamyl transpeptidase GGT4 initiates vacuolar degradation of glutathione S-conjugates in Arabidopsis. FEBS Lett. 581 (2007) 3131–3138. [PMID: 17561001]
8.	Wickham, S., West, M.B., Cook, P.F. and Hanigan, M.H. Gamma-glutamyl compounds: substrate specificity of γ-glutamyl transpeptidase enzymes. Anal. Biochem. 414 (2011) 208–214. [DOI] [PMID: 21447318]
9.	Keillor, J.W., Castonguay, R. and Lherbet, C. Gamma-glutamyl transpeptidase substrate specificity and catalytic mechanism. Methods Enzymol. 401 (2005) 449–467. [PMID: 16399402]

[EC 3.4.19.13 created 2011, modified 2019]

*EC

3.4.22.68

Accepted name:

Ulp1 peptidase

Reaction:

Hydrolysis of the α-linked peptide bond in the sequence Gly-Gly┼Ala-Thr-Tyr at the C-terminal end of the small ubiquitin-like modifier (SUMO) propeptide, Smt3, leading to the mature form of the protein. A second reaction involves the cleavage of an ε-linked peptide bond between the C-terminal glycine of the mature SUMO and the lysine ε-amino group of the target protein

Other name(s):

Smt3-protein conjugate proteinase; Ubl-specific protease 1; Ulp1; Ulp1 endopeptidase; Ulp1 protease

Comments:

The enzyme from Saccharomyces cerevisiae can also recognize small ubiquitin-like modifier 1 (SUMO-1) from human as a substrate in both SUMO-processing (α-linked peptide bonds) and SUMO-deconjugation (ε-linked peptide bonds) reactions [1,2,3]. Ulp1 has several functions, including an essential role in chromosomal segregation and progression of the cell cycle through the G2/M phase of the cell cycle. Belongs in peptidase family C48.

Links to other databases:

References:

1.	Lima, C.D. Ulp1 endopeptidase. In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Ed.), Handbook of Proteolytic Enzymes, 2nd edn, Elsevier, London, 2004, pp. 1340–1344.
2.	Li, S.-J. and Hochstrasser, M. A new protease required for cell-cycle progression in yeast. Nature 398 (1999) 246–251. [DOI] [PMID: 10094048]
3.	Taylor, D.L., Ho, J.C., Oliver, A. and Watts, F.Z. Cell-cycle-dependent localisation of Ulp1, a Schizosaccharomyces pombe Pmt3 (SUMO)-specific protease. J. Cell Sci. 115 (2002) 1113–1122. [PMID: 11884512]
4.	Li, S.-J. and Hochstrasser, M. The Ulp1 SUMO isopeptidase: distinct domains required for viability, nuclear envelope localization, and substrate specificity. J. Cell Biol. 160 (2003) 1069–1081. [DOI] [PMID: 12654900]
5.	Ihara, M., Koyama, H., Uchimura, Y., Saitoh, H. and Kikuchi, A. Noncovalent binding of small ubiquitin-related modifier (SUMO) protease to SUMO is necessary for enzymatic activities and cell growth. J. Biol. Chem. 282 (2007) 16465–16475. [DOI] [PMID: 17428805]
6.	Mukhopadhyay, D. and Dasso, M. Modification in reverse: the SUMO proteases. Trends Biochem. Sci. 32 (2007) 286–295. [DOI] [PMID: 17499995]

[EC 3.4.22.68 created 2008, modified 2011]

3.4.23.52

Accepted name:

preflagellin peptidase

Reaction:

Cleaves the signal peptide of 3 to 12 amino acids from the N-terminal of preflagellin, usually at Arg-Gly┼ or Lys-Gly┼, to release flagellin.

Other name(s):

FlaK

Comments:

An aspartic peptidase from Archaea but not bacteria. In peptidase family A24 (type IV prepilin peptidase family).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, MEROPS, PDB

References:

1.	Bardy, S.L. and Jarrell, K.F. FlaK of the archaeon Methanococcus maripaludis possesses preflagellin peptidase activity. FEMS Microbiol. Lett. 208 (2002) 53–59. [DOI] [PMID: 11934494]
2.	Ng, S.Y., VanDyke, D.J., Chaban, B., Wu, J., Nosaka, Y., Aizawa, S. and Jarrell, K.F. Different minimal signal peptide lengths recognized by the archaeal prepilin-like peptidases FlaK and PibD. J. Bacteriol. 191 (2009) 6732–6740. [DOI] [PMID: 19717585]
3.	Hu, J., Xue, Y., Lee, S. and Ha, Y. The crystal structure of GXGD membrane protease FlaK. Nature 475 (2011) 528–531. [DOI] [PMID: 21765428]

[EC 3.4.23.52 created 2011]

*EC

3.5.1.94

Accepted name:

γ-glutamyl-γ-aminobutyrate hydrolase

Reaction:

4-(γ-L-glutamylamino)butanoate + H₂O = 4-aminobutanoate + L-glutamate

Glossary:

4-aminobutanoate = γ-aminobutyrate = GABA

Other name(s):

γ-glutamyl-GABA hydrolase; PuuD; YcjL; 4-(γ-glutamylamino)butanoate amidohydrolase; 4-(L-γ-glutamylamino)butanoate amidohydrolase

Systematic name:

4-(γ-L-glutamylamino)butanoate amidohydrolase

Comments:

Forms part of a putrescine-utilizing pathway in Escherichia coli, in which it has been hypothesized that putrescine is first glutamylated to form γ-glutamylputrescine, which is oxidized to 4-(γ-glutamylamino)butanal and then to 4-(γ-glutamylamino)butanoate. The enzyme can also catalyse the reactions of EC 3.5.1.35 (D-glutaminase) and EC 3.5.1.65 (theanine hydrolase).

Links to other databases:

References:

1.	Kurihara, S., Oda, S., Kato, K., Kim, H.G., Koyanagi, T., Kumagai, H. and Suzuki, H. A novel putrescine utilization pathway involves γ-glutamylated intermediates of Escherichia coli K-12. J. Biol. Chem. 280 (2005) 4602–4608. [DOI] [PMID: 15590624]

[EC 3.5.1.94 created 2006, modified 2011]

3.5.1.109

Accepted name:

sphingomyelin deacylase

Reaction:

(1) an N-acyl-sphingosylphosphorylcholine + H₂O = a fatty acid + sphingosylphosphorylcholine
(2) a D-glucosyl-N-acylsphingosine + H₂O = a fatty acid + D-glucosyl-sphingosine

Glossary:

sphingomyelin = N-acyl-sphingosylphosphorylcholine
D-glucosyl-N-acylsphingosine = glucosylceramide

Other name(s):

SM deacylase; GcSM deacylase; glucosylceramide sphingomyelin deacylase; sphingomyelin glucosylceramide deacylase; SM glucosylceramide GCer deacylase; SM-GCer deacylase; SMGCer deacylase

Systematic name:

N-acyl-sphingosylphosphorylcholine amidohydrolase

Comments:

The enzyme is involved in the sphingolipid metabolism in the epidermis.

Links to other databases:

References:

1.	Hara, J., Higuchi, K., Okamoto, R., Kawashima, M. and Imokawa, G. High-expression of sphingomyelin deacylase is an important determinant of ceramide deficiency leading to barrier disruption in atopic dermatitis. J. Invest. Dermatol. 115 (2000) 406–413. [DOI] [PMID: 10951276]
2.	Higuchi, K., Hara, J., Okamoto, R., Kawashima, M. and Imokawa, G. The skin of atopic dermatitis patients contains a novel enzyme, glucosylceramide sphingomyelin deacylase, which cleaves the N-acyl linkage of sphingomyelin and glucosylceramide. Biochem. J. 350 (2000) 747–756. [PMID: 10970788]
3.	Ishibashi, M., Arikawa, J., Okamoto, R., Kawashima, M., Takagi, Y., Ohguchi, K. and Imokawa, G. Abnormal expression of the novel epidermal enzyme, glucosylceramide deacylase, and the accumulation of its enzymatic reaction product, glucosylsphingosine, in the skin of patients with atopic dermatitis. Lab. Invest. 83 (2003) 397–408. [PMID: 12649340]

[EC 3.5.1.109 created 2011]

*EC

3.5.99.2

Accepted name:

aminopyrimidine aminohydrolase

Reaction:

(1) 4-amino-5-aminomethyl-2-methylpyrimidine + H₂O = 4-amino-5-hydroxymethyl-2-methylpyrimidine + NH₃
(2) thiamine + H₂O = 4-amino-5-hydroxymethyl-2-methylpyrimidine + 5-(2-hydroxyethyl)-4-methylthiazole

Other name(s):

thiaminase (ambiguous); thiaminase II; tenA (gene name)

Systematic name:

4-amino-5-aminomethyl-2-methylpyrimidine aminohydrolase

Comments:

Previously known as thiaminase II, this enzyme is involved in the regeneration of the thiamine pyrimidine from degraded products, rather than in thiamine degradation, and participates in thiamine salvage pathways.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 9024-80-0

References:

1.	Fujita, A., Nose, Y. and Kuratani, K. Second type of bacterial thiaminase. J. Vitaminol. (Kyoto) 1 (1954) 1–7. [PMID: 13243520]
2.	Ikehata, H. Purification of thiaminase II. J. Gen. Appl. Microbiol. 6 (1960) 30–39.
3.	Toms, A.V., Haas, A.L., Park, J.H., Begley, T.P. and Ealick, S.E. Structural characterization of the regulatory proteins TenA and TenI from Bacillus subtilis and identification of TenA as a thiaminase II. Biochemistry 44 (2005) 2319–2329. [DOI] [PMID: 15709744]
4.	Benach, J., Edstrom, W.C., Lee, I., Das, K., Cooper, B., Xiao, R., Liu, J., Rost, B., Acton, T.B., Montelione, G.T. and Hunt, J.F. The 2.35 Å structure of the TenA homolog from Pyrococcus furiosus supports an enzymatic function in thiamine metabolism. Acta Crystallogr. D Biol. Crystallogr. 61 (2005) 589–598. [DOI] [PMID: 15858269]
5.	Jenkins, A.H., Schyns, G., Potot, S., Sun, G. and Begley, T.P. A new thiamin salvage pathway. Nat. Chem. Biol. 3 (2007) 492–497. [DOI] [PMID: 17618314]
6.	Jenkins, A.L., Zhang, Y., Ealick, S.E. and Begley, T.P. Mutagenesis studies on TenA: a thiamin salvage enzyme from Bacillus subtilis. Bioorg. Chem. 36 (2008) 29–32. [DOI] [PMID: 18054064]
7.	French, J.B., Begley, T.P. and Ealick, S.E. Structure of trifunctional THI20 from yeast. Acta Crystallogr. D Biol. Crystallogr. 67 (2011) 784–791. [DOI] [PMID: 21904031]

[EC 3.5.99.2 created 1961, modified 2011]

3.6.1.55

Accepted name:

8-oxo-dGTP diphosphatase

Reaction:

8-oxo-dGTP + H₂O = 8-oxo-dGMP + diphosphate

Glossary:

8-oxo-dGTP = 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate

Other name(s):

MutT; 7,8-dihydro-8-oxoguanine triphosphatase; 8-oxo-dGTPase; 7,8-dihydro-8-oxo-dGTP pyrophosphohydrolase

Systematic name:

8-oxo-dGTP diphosphohydrolase

Comments:

This enzyme hydrolyses the phosphoanhydride bond between the α and β phosphate of 8-oxoguanine-containing nucleoside di- and triphosphates thereby preventing misincorporation of the oxidized purine nucleoside triphosphates into DNA. It does not hydrolyse 2-hydroxy-dATP (cf. EC 3.6.1.56, 2-hydroxy-dATP diphosphatase) [4]. Requires Mg²⁺.

Links to other databases:

References:

1.	Ito, R., Hayakawa, H., Sekiguchi, M. and Ishibashi, T. Multiple enzyme activities of Escherichia coli MutT protein for sanitization of DNA and RNA precursor pools. Biochemistry 44 (2005) 6670–6674. [DOI] [PMID: 15850400]
2.	Yoshimura, K., Ogawa, T., Ueda, Y. and Shigeoka, S. AtNUDX1, an 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate pyrophosphohydrolase, is responsible for eliminating oxidized nucleotides in Arabidopsis. Plant Cell Physiol. 48 (2007) 1438–1449. [DOI] [PMID: 17804481]
3.	Nakamura, T., Meshitsuka, S., Kitagawa, S., Abe, N., Yamada, J., Ishino, T., Nakano, H., Tsuzuki, T., Doi, T., Kobayashi, Y., Fujii, S., Sekiguchi, M. and Yamagata, Y. Structural and dynamic features of the MutT protein in the recognition of nucleotides with the mutagenic 8-oxoguanine base. J. Biol. Chem. 285 (2010) 444–452. [DOI] [PMID: 19864691]
4.	Yonekura, S., Sanada, U. and Zhang-Akiyama, Q.M. CiMutT, an asidian MutT homologue, has a 7, 8-dihydro-8-oxo-dGTP pyrophosphohydrolase activity responsible for sanitization of oxidized nucleotides in Ciona intestinalis. Genes Genet. Syst. 85 (2010) 287–295. [PMID: 21178309]

[EC 3.6.1.55 created 2011]

3.6.1.56

Accepted name:

2-hydroxy-dATP diphosphatase

Reaction:

2-hydroxy-dATP + H₂O = 2-hydroxy-dAMP + diphosphate

Other name(s):

NUDT1; MTH1; MTH₂; oxidized purine nucleoside triphosphatase; (2′-deoxy) ribonucleoside 5′-triphosphate pyrophosphohydrolase

Systematic name:

2-hydroxy-dATP diphosphohydrolase

Comments:

The enzyme hydrolyses oxidized purine nucleoside triphosphates such as 2-hydroxy-dATP, thereby preventing their misincorporation into DNA. It can also recognize 8-oxo-dGTP and 8-oxo-dATP, but with lower efficiency (cf. EC 3.6.1.55, 8-oxo-dGTP diphosphatase) [3].

Links to other databases:

References:

1.	Sakumi, K., Furuichi, M., Tsuzuki, T., Kakuma, T., Kawabata, S., Maki, H. and Sekiguchi, M. Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis. J. Biol. Chem. 268 (1993) 23524–23530. [PMID: 8226881]
2.	Kakuma, T., Nishida, J., Tsuzuki, T. and Sekiguchi, M. Mouse MTH1 protein with 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphatase activity that prevents transversion mutation. cDNA cloning and tissue distribution. J. Biol. Chem. 270 (1995) 25942–25948. [DOI] [PMID: 7592783]
3.	Fujikawa, K., Kamiya, H., Yakushiji, H., Fujii, Y., Nakabeppu, Y. and Kasai, H. The oxidized forms of dATP are substrates for the human MutT homologue, the hMTH1 protein. J. Biol. Chem. 274 (1999) 18201–18205. [DOI] [PMID: 10373420]
4.	Sakai, Y., Furuichi, M., Takahashi, M., Mishima, M., Iwai, S., Shirakawa, M. and Nakabeppu, Y. A molecular basis for the selective recognition of 2-hydroxy-dATP and 8-oxo-dGTP by human MTH1. J. Biol. Chem. 277 (2002) 8579–8587. [DOI] [PMID: 11756418]
5.	Fujikawa, K., Kamiya, H., Yakushiji, H., Nakabeppu, Y. and Kasai, H. Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP. Nucleic Acids Res. 29 (2001) 449–454. [DOI] [PMID: 11139615]

[EC 3.6.1.56 created 2011]

3.6.1.57

Accepted name:

UDP-2,4-diacetamido-2,4,6-trideoxy-β-L-altropyranose hydrolase

Reaction:

UDP-2,4-diacetamido-2,4,6-trideoxy-β-L-altropyranose + H₂O = 2,4-diacetamido-2,4,6-trideoxy-β-L-altropyranose + UDP

Glossary:

pseudaminic acid = 5,7-diacetylamino-3,5,7,9-tetradeoxy-L-glycero-α-L-manno-2-nonulopyranosonic acid

Other name(s):

PseG; UDP-6-deoxy-AltdiNAc hydrolase; Cj1312; UDP-2,4-bis(acetamido)-2,4,6-trideoxy-β-L-altropyranose hydrolase

Systematic name:

UDP-2,4-diacetamido-2,4,6-trideoxy-β-L-altropyranose hydrolase

Comments:

The enzyme is involved in biosynthesis of pseudaminic acid.

Links to other databases:

References:

1.	Liu, F. and Tanner, M.E. PseG of pseudaminic acid biosynthesis: a UDP-sugar hydrolase as a masked glycosyltransferase. J. Biol. Chem. 281 (2006) 20902–20909. [DOI] [PMID: 16728396]
2.	Schoenhofen, I.C., McNally, D.J., Brisson, J.R. and Logan, S.M. Elucidation of the CMP-pseudaminic acid pathway in Helicobacter pylori: synthesis from UDP-N-acetylglucosamine by a single enzymatic reaction. Glycobiology 16 (2006) 8C–14C. [DOI] [PMID: 16751642]

[EC 3.6.1.57 created 2011]

*EC

3.6.3.8

Transferred entry:

Ca²⁺-transporting ATPase. Now EC 7.2.2.10, Ca²⁺-transporting ATPase

[EC 3.6.3.8 created 1984 as EC 3.6.1.38, transferred 2000 to EC 3.6.3.8, modified 2001, modified 2011, deleted 2018]

3.7.1.14

Accepted name:

2-hydroxy-6-oxonona-2,4-dienedioate hydrolase

Reaction:

(1) (2Z,4E)-2-hydroxy-6-oxonona-2,4-diene-1,9-dioate + H₂O = (2Z)-2-hydroxypenta-2,4-dienoate + succinate
(2) (2Z,4E,7E)-2-hydroxy-6-oxonona-2,4,7-triene-1,9-dioate + H₂O = (2Z)-2-hydroxypenta-2,4-dienoate + fumarate

For diagram of 3-phenylpropanoate catabolism, click here and for diagram of cinnamate catabolism, click here

Other name(s):

mhpC (gene name)

Systematic name:

(2Z,4E)-2-hydroxy-6-oxona-2,4-dienedioate succinylhydrolase

Comments:

This enzyme catalyses a step in a pathway of phenylpropanoid compounds degradation. The first step of the enzyme mechanism involves a reversible keto-enol tautomerization [4].

Links to other databases:

References:

1.	Burlingame, R. and Chapman, P.J. Catabolism of phenylpropionic acid and its 3-hydroxy derivative by Escherichia coli. J. Bacteriol. 155 (1983) 113–121. [PMID: 6345502]
2.	Burlingame, R.P., Wyman, L. and Chapman, P.J. Isolation and characterization of Escherichia coli mutants defective for phenylpropionate degradation. J. Bacteriol. 168 (1986) 55–64. [DOI] [PMID: 3531186]
3.	Lam, W. W. Y and Bugg, T. D. H. Chemistry of extradiol aromatic ring cleavage: isolation of a stable dienol ring fission intermediate and stereochemistry of its enzymatic hydrolytic clevage. J. Chem. Soc., Chem. Commun. 10 (1994) 1163–1164.
4.	Lam, W.W. and Bugg, T.D. Purification, characterization, and stereochemical analysis of a C-C hydrolase: 2-hydroxy-6-keto-nona-2,4-diene-1,9-dioic acid 5,6-hydrolase. Biochemistry 36 (1997) 12242–12251. [DOI] [PMID: 9315862]
5.	Ferrández, A., García, J.L. and Díaz, E. Genetic characterization and expression in heterologous hosts of the 3-(3-hydroxyphenyl)propionate catabolic pathway of Escherichia coli K-12. J. Bacteriol. 179 (1997) 2573–2581. [DOI] [PMID: 9098055]
6.	Díaz, E., Ferrández, A. and García, J.L. Characterization of the hca cluster encoding the dioxygenolytic pathway for initial catabolism of 3-phenylpropionic acid in Escherichia coli K-12. J. Bacteriol. 180 (1998) 2915–2923. [PMID: 9603882]

[EC 3.7.1.14 created 2011, modified 2012]

3.7.1.15

Transferred entry:

(+)-caryolan-1-ol synthase. Now EC 4.2.1.138, (+)-caryolan-1-ol synthase

[EC 3.7.1.15 created 2011, deleted 2013]

3.7.1.16

Transferred entry:

oxepin-CoA hydrolase. Now EC 3.3.2.12, oxepin-CoA hydrolase

[EC 3.7.1.16 created 2011, deleted 2013]

*EC

4.1.1.77

Accepted name:

2-oxo-3-hexenedioate decarboxylase

Reaction:

(3E)-2-oxohex-3-enedioate = 2-oxopent-4-enoate + CO₂

For diagram of catechol catabolism (meta ring cleavage), click here

Other name(s):

4-oxalocrotonate carboxy-lyase (misleading); 4-oxalocrotonate decarboxylase (misleading); cnbF (gene name); praD (gene name); amnE (gene name); nbaG (gene name); xylI (gene name)

Systematic name:

(3E)-2-oxohex-3-enedioate carboxy-lyase (2-oxopent-4-enoate-forming)

Comments:

Involved in the meta-cleavage pathway for the degradation of phenols, modified phenols and catechols. The enzyme has been reported to accept multiple tautomeric forms [1-4]. However, careful analysis of the stability of the different tautomers, as well as characterization of the enzyme that produces its substrate, EC 5.3.2.6, 2-hydroxymuconate tautomerase, showed that the actual substrate for the enzyme is (3E)-2-oxohex-3-enedioate [4].

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 37325-55-6

References:

1.	Shingler, V., Marklund, U., Powlowski, J. Nucleotide sequence and functional analysis of the complete phenol/3,4-dimethylphenol catabolic pathway of Pseudomonas sp. strain CF600. J. Bacteriol. 174 (1992) 711–724. [DOI] [PMID: 1732207]
2.	Takenaka, S., Murakami, S., Shinke, R. and Aoki, K. Metabolism of 2-aminophenol by Pseudomonas sp. AP-3: modified meta-cleavage pathway. Arch. Microbiol. 170 (1998) 132–137. [PMID: 9683650]
3.	Stanley, T.M., Johnson, W.H., Jr., Burks, E.A., Whitman, C.P., Hwang, C.C. and Cook, P.F. Expression and stereochemical and isotope effect studies of active 4-oxalocrotonate decarboxylase. Biochemistry 39 (2000) 718–726. [DOI] [PMID: 10651637]
4.	Wang, S.C., Johnson, W.H., Jr., Czerwinski, R.M., Stamps, S.L. and Whitman, C.P. Kinetic and stereochemical analysis of YwhB, a 4-oxalocrotonate tautomerase homologue in Bacillus subtilis: mechanistic implications for the YwhB- and 4-oxalocrotonate tautomerase-catalyzed reactions. Biochemistry 46 (2007) 11919–11929. [DOI] [PMID: 17902707]
5.	Kasai, D., Fujinami, T., Abe, T., Mase, K., Katayama, Y., Fukuda, M. and Masai, E. Uncovering the protocatechuate 2,3-cleavage pathway genes. J. Bacteriol. 191 (2009) 6758–6768. [DOI] [PMID: 19717587]

[EC 4.1.1.77 created 1999, modified 2011, modified 2012]

4.1.1.93

Accepted name:

pyrrole-2-carboxylate decarboxylase

Reaction:

(1) pyrrole-2-carboxylate = pyrrole + CO₂
(2) pyrrole-2-carboxylate + H₂O = pyrrole + HCO₃^-

Systematic name:

pyrrole-2-carboxylate carboxy-lyase

Comments:

The enzyme catalyses both the carboxylation and decarboxylation reactions. However, while bicarbonate is the preferred substrate for the carboxylation reaction, decarboxylation produces carbon dioxide. The enzyme is activated by carboxylic acids.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, KEGG, PDB

References:

1.	Wieser, M., Fujii, N., Yoshida, T. and Nagasawa, T. Carbon dioxide fixation by reversible pyrrole-2-carboxylate decarboxylase from Bacillus megaterium PYR2910. Eur. J. Biochem. 257 (1998) 495–499. [DOI] [PMID: 9826198]
2.	Omura, H., Wieser, M. and Nagasawa, T. Pyrrole-2-carboxylate decarboxylase from Bacillus megaterium PYR2910, an organic-acid-requiring enzyme. Eur. J. Biochem. 253 (1998) 480–484. [DOI] [PMID: 9654100]
3.	Wieser, M., Yoshida, T. and Nagasawa, T. Microbial synthesis of pyrrole-2-carboxylate by Bacillus megaterium PYR2910. Tetrahedron Lett. 39 (1998) 4309–4310.

[EC 4.1.1.93 created 2011]

*EC

4.1.2.5

Accepted name:

L-threonine aldolase

Reaction:

L-threonine = glycine + acetaldehyde

Other name(s):

L-threonine acetaldehyde-lyase

Systematic name:

L-threonine acetaldehyde-lyase (glycine-forming)

Comments:

A pyridoxal-phosphate protein. This enzyme is specific for L-threonine and can not utilize L-allo-threonine. Different from EC 4.1.2.49, L-allo-threonine aldolase, and EC 4.1.2.48, low-specificity L-threonine aldolase.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 62213-23-4

References:

1.	Dainty, R.H. Purification and properties of threonine aldolase from Clostridium pasteurianum. Biochem. J. 117 (1970) 585–592. [PMID: 5419751]
2.	Karasek, M.A. and Greenberg, D.M. Studies on the properties of threonine aldolases. J. Biol. Chem. 227 (1957) 191–205. [PMID: 13449064]

[EC 4.1.2.5 created 1961, deleted 1972, reinstated 1976, modified 2011]

4.1.2.48

Accepted name:

low-specificity L-threonine aldolase

Reaction:

(1) L-threonine = glycine + acetaldehyde
(2) L-allo-threonine = glycine + acetaldehyde

Other name(s):

LtaE

Systematic name:

L-threonine/L-allo-threonine acetaldehyde-lyase (glycine-forming)

Comments:

Requires pyridoxal phosphate. The low-specificity L-threonine aldolase can act on both L-threonine and L-allo-threonine [1,2]. The enzyme from Escherichia coli can also act on L-threo-phenylserine and L-erythro-phenylserine [4]. The enzyme can also catalyse the aldol condensation of glycolaldehyde and glycine to form 4-hydroxy-L-threonine, an intermediate of pyridoxal phosphate biosynthesis [3]. Different from EC 4.1.2.5, L-threonine aldolase, and EC 4.1.2.49, L-allo-threonine aldolase.

Links to other databases:

References:

1.	Yamada, H., Kumagai, H., Nagate, T. and Yoshida, H. Crystalline threonine aldolase from Candida humicola. Biochem. Biophys. Res. Commun. 39 (1970) 53–58. [DOI] [PMID: 5438301]
2.	Kumagai, H., Nagate, T., Yoshida, H. and Yamada, H. Threonine aldolase from Candida humicola. II. Purification, crystallization and properties. Biochim. Biophys. Acta 258 (1972) 779–790. [DOI] [PMID: 5017702]
3.	Liu, J.Q., Nagata, S., Dairi, T., Misono, H., Shimizu, S. and Yamada, H. The GLY1 gene of Saccharomyces cerevisiae encodes a low-specific L-threonine aldolase that catalyzes cleavage of L-allo-threonine and L-threonine to glycine—expression of the gene in Escherichia coli and purification and characterization of the enzyme. Eur. J. Biochem. 245 (1997) 289–293. [DOI] [PMID: 9151955]
4.	Liu, J.Q., Dairi, T., Itoh, N., Kataoka, M., Shimizu, S. and Yamada, H. Gene cloning, biochemical characterization and physiological role of a thermostable low-specificity L-threonine aldolase from Escherichia coli. Eur. J. Biochem. 255 (1998) 220–226. [DOI] [PMID: 9692922]
5.	Kim, J., Kershner, J.P., Novikov, Y., Shoemaker, R.K. and Copley, S.D. Three serendipitous pathways in E. coli can bypass a block in pyridoxal-5′-phosphate synthesis. Mol. Syst. Biol. 6:436 (2010). [DOI] [PMID: 21119630]

[EC 4.1.2.48 created 2011]

4.1.2.49

Accepted name:

L-allo-threonine aldolase

Reaction:

L-allo-threonine = glycine + acetaldehyde

Systematic name:

L-allo-threonine acetaldehyde-lyase (glycine-forming)

Comments:

Requires pyridoxal phosphate. This enzyme, characterized from the bacterium Aeromonas jandaei, is specific for L-allo-threonine and can not act on either L-threonine or L-serine. Different from EC 4.1.2.5, L-threonine aldolase, and EC 4.1.2.48, low-specificity L-threonine aldolase. A previously listed enzyme with this name, EC 4.1.2.6, was deleted in 1971 after it was found to be identical to EC 2.1.2.1, glycine hydroxymethyltransferase.

Links to other databases:

References:

1.	Kataoka, M., Wada, M., Nishi, K., Yamada, H. and Shimizu, S. Purification and characterization of L-allo-threonine aldolase from Aeromonas jandaei DK-39. FEMS Microbiol. Lett. 151 (1997) 245–248. [DOI] [PMID: 9228760]

[EC 4.1.2.49 created 2011]

4.1.99.17

Accepted name:

phosphomethylpyrimidine synthase

Reaction:

5-amino-1-(5-phospho-D-ribosyl)imidazole + S-adenosyl-L-methionine = 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + 5′-deoxyadenosine + L-methionine + formate + CO

For diagram of thiamine diphosphate biosynthesis, click here

Other name(s):

thiC (gene name)

Systematic name:

5-amino-1-(5-phospho-D-ribosyl)imidazole formate-lyase (decarboxylating, 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine-forming)

Comments:

Binds a [4Fe-4S] cluster that is coordinated by 3 cysteines and an exchangeable S-adenosyl-L-methionine molecule. The first stage of catalysis is reduction of the S-adenosyl-L-methionine to produce L-methionine and a 5′-deoxyadenosin-5′-yl radical that is crucial for the conversion of the substrate. Part of the pathway for thiamine biosynthesis.

Links to other databases:

References:

1.	Chatterjee, A., Li, Y., Zhang, Y., Grove, T.L., Lee, M., Krebs, C., Booker, S.J., Begley, T.P. and Ealick, S.E. Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily. Nat. Chem. Biol. 4 (2008) 758–765. [DOI] [PMID: 18953358]
2.	Martinez-Gomez, N.C., Poyner, R.R., Mansoorabadi, S.O., Reed, G.H. and Downs, D.M. Reaction of AdoMet with ThiC generates a backbone free radical. Biochemistry 48 (2009) 217–219. [DOI] [PMID: 19113839]
3.	Chatterjee, A., Hazra, A.B., Abdelwahed, S., Hilmey, D.G. and Begley, T.P. A "radical dance" in thiamin biosynthesis: mechanistic analysis of the bacterial hydroxymethylpyrimidine phosphate synthase. Angew. Chem. Int. Ed. Engl. 49 (2010) 8653–8656. [DOI] [PMID: 20886485]

[EC 4.1.99.17 created 2011]

4.1.99.18

Transferred entry:

cyclic pyranopterin phosphate synthase. Now known to be catalysed by the combined effort of EC 4.1.99.22, GTP 3,8-cyclase, and EC 4.6.1.17, cyclic pyranopterin monophosphate synthase

[EC 4.1.99.18 created 2011, deleted 2016]

4.1.99.19

Accepted name:

2-iminoacetate synthase

Reaction:

L-tyrosine + S-adenosyl-L-methionine + NADPH = 2-iminoacetate + 4-methylphenol + 5′-deoxyadenosine + L-methionine + NADP⁺ + H⁺

For diagram of thiamine diphosphate biosynthesis, click here

Glossary:

4-methylphenol = 4-cresol = p-cresol

Other name(s):

thiH (gene name)

Systematic name:

L-tyrosine 4-methylphenol-lyase (2-iminoacetate-forming)

Comments:

Binds a [4Fe-4S] cluster that is coordinated by 3 cysteines and an exchangeable S-adenosyl-L-methionine molecule. The first stage of catalysis is reduction of the S-adenosyl-L-methionine to produce methionine and a 5-deoxyadenosin-5-yl radical that is crucial for the conversion of the substrate. The reductant is assumed to be NADPH, which is provided by a flavoprotein:NADPH oxidoreductase system [4]. Part of the pathway for thiamine biosynthesis.

Links to other databases:

References:

1.	Leonardi, R., Fairhurst, S.A., Kriek, M., Lowe, D.J. and Roach, P.L. Thiamine biosynthesis in Escherichia coli: isolation and initial characterisation of the ThiGH complex. FEBS Lett. 539 (2003) 95–99. [DOI] [PMID: 12650933]
2.	Kriek, M., Martins, F., Challand, M.R., Croft, A. and Roach, P.L. Thiamine biosynthesis in Escherichia coli: identification of the intermediate and by-product derived from tyrosine. Angew. Chem. Int. Ed. Engl. 46 (2007) 9223–9226. [DOI] [PMID: 17969213]
3.	Kriek, M., Martins, F., Leonardi, R., Fairhurst, S.A., Lowe, D.J. and Roach, P.L. Thiazole synthase from Escherichia coli: an investigation of the substrates and purified proteins required for activity in vitro. J. Biol. Chem. 282 (2007) 17413–17423. [DOI] [PMID: 17403671]
4.	Challand, M.R., Martins, F.T. and Roach, P.L. Catalytic activity of the anaerobic tyrosine lyase required for thiamine biosynthesis in Escherichia coli. J. Biol. Chem. 285 (2010) 5240–5248. [DOI] [PMID: 19923213]

[EC 4.1.99.19 created 2011, modified 2014]

*EC

4.2.1.20

Accepted name:

tryptophan synthase

Reaction:

L-serine + 1-C-(indol-3-yl)glycerol 3-phosphate = L-tryptophan + D-glyceraldehyde 3-phosphate + H₂O (overall reaction)
(1a) 1-C-(indol-3-yl)glycerol 3-phosphate = indole + D-glyceraldehyde 3-phosphate
(1b) L-serine + indole = L-tryptophan + H₂O

For diagram of tryptophan biosynthesis, click here

Other name(s):

L-tryptophan synthetase; indoleglycerol phosphate aldolase; tryptophan desmolase; tryptophan synthetase; L-serine hydro-lyase (adding indoleglycerol-phosphate); L-serine hydro-lyase [adding 1-C-(indol-3-yl)glycerol 3-phosphate, L-tryptophan and glyceraldehyde-3-phosphate-forming]

Systematic name:

L-serine hydro-lyase [adding 1-C-(indol-3-yl)glycerol 3-phosphate, L-tryptophan and D-glyceraldehyde-3-phosphate-forming]

Comments:

A pyridoxal-phosphate protein. The α-subunit catalyses the conversion of 1-C-(indol-3-yl)glycerol 3-phosphate to indole and D-glyceraldehyde 3-phosphate (this reaction was included formerly under EC 4.1.2.8). The indole migrates to the β-subunit where, in the presence of pyridoxal 5′-phosphate, it is combined with L-serine to form L-tryptophan. In some organisms this enzyme is part of a multifunctional protein that also includes one or more of the enzymes EC 2.4.2.18 (anthranilate phosphoribosyltransferase), EC 4.1.1.48 (indole-3-glycerol-phosphate synthase), EC 4.1.3.27 (anthranilate synthase) and EC 5.3.1.24 (phosphoribosylanthranilate isomerase). In thermophilic organisms, where the high temperature enhances diffusion and causes the loss of indole, a protein similar to the β subunit can be found (EC 4.2.1.122). That enzyme cannot combine with the α unit of EC 4.2.1.20 to form a complex.

Links to other databases:

BRENDA, EXPASY, Gene, GTD, KEGG, PDB, CAS registry number: 9014-52-2

References:

1.	Crawford, I.P. and Yanofsky, C. On the separation of the tryptophan synthetase of Escherichia coli into two protein components. Proc. Natl. Acad. Sci. USA 44 (1958) 1161–1170. [DOI] [PMID: 16590328]
2.	Creighton, T.E. and Yanofsky, C. Chorismate to tryptophan (Escherichia coli) - anthranilate synthetase, PR transferase, PRA isomerase, InGP synthetase, tryptophan synthetase. Methods Enzymol. 17A (1970) 365–380.
3.	Hütter, R., Niederberger, P. and DeMoss, J.A. Tryptophan synthetic genes in eukaryotic microorganisms. Annu. Rev. Microbiol. 40 (1986) 55–77. [DOI] [PMID: 3535653]
4.	Hyde, C.C., Ahmed, S.A., Padlan, E.A., Miles, E.W. and Davies, D.R. Three-dimensional structure of the tryptophan synthase α2β2 multienzyme complex from Salmonella typhimurium. J. Biol. Chem. 263 (1988) 17857–17871. [PMID: 3053720]
5.	Woehl, E. and Dunn, M.F. Mechanisms of monovalent cation action in enzyme catalysis: the tryptophan synthase α-, β-, and αβ-reactions. Biochemistry 38 (1999) 7131–7141. [DOI] [PMID: 10353823]

[EC 4.2.1.20 created 1961, modified 1976, modified 2002, modified 2011]

*EC

4.2.1.83

Accepted name:

4-oxalomesaconate hydratase

Reaction:

2-hydroxy-4-oxobutane-1,2,4-tricarboxylate = (1E,3E)-4-hydroxybuta-1,3-diene-1,2,4-tricarboxylate + H₂O

For diagram of the protocatechuate 3,4-cleavage pathway, click here

Other name(s):

4-oxalmesaconate hydratase; 4-carboxy-2-oxohexenedioate hydratase; 4-carboxy-2-oxobutane-1,2,4-tricarboxylate 2,3-hydro-lyase; oxalmesaconate hydratase; γ-oxalmesaconate hydratase; 2-hydroxy-4-oxobutane-1,2,4-tricarboxylate 2,3-hydro-lyase; LigJ; GalB

Systematic name:

(1E,3E)-4-hydroxybuta-1,3-diene-1,2,4-tricarboxylate 1,2-hydro-lyase (2-hydroxy-4-oxobutane-1,2,4-tricarboxylate-forming)

Comments:

This enzyme participates in the degradation of 3,4-dihydroxybenzoate (via the meta-cleavage pathway), syringate and 3,4,5-trihydroxybenzoate, catalysing the reaction in the opposite direction [1-3]. It accepts the enol-form of 4-oxalomesaconate, 2-hydroxy-4-carboxy-hexa-2,4-dienedioate [4].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 85204-95-1

References:

1.	Maruyama, K. Enzymes responsible for degradation of 4-oxalmesaconic acid in Pseudomonas ochraceae. J. Biochem. 93 (1983) 567–574. [PMID: 6841354]
2.	Maruyama, K. Purification and properties of γ-oxalomesaconate hydratase from Pseudomonas ochraceae grown with phthalate. Biochem. Biophys. Res. Commun. 128 (1985) 271–277. [DOI] [PMID: 3985968]
3.	Hara, H., Masai, E., Katayama, Y. and Fukuda, M. The 4-oxalomesaconate hydratase gene, involved in the protocatechuate 4,5-cleavage pathway, is essential to vanillate and syringate degradation in Sphingomonas paucimobilis SYK-6. J. Bacteriol. 182 (2000) 6950–6957. [DOI] [PMID: 11092855]
4.	Nogales, J., Canales, A., Jiménez-Barbero, J., Serra B., Pingarrón, J. M., García, J. L. and Díaz, E. Unravelling the gallic acid degradation pathway in bacteria: the gal cluster from Pseudomonas putida. Mol. Microbiol. 79 (2011) 359–374. [DOI] [PMID: 21219457]

[EC 4.2.1.83 created 1986, modified 2011]

4.2.1.130

Accepted name:

D-lactate dehydratase

Reaction:

(R)-lactate = 2-oxopropanal + H₂O

Glossary:

methylglyoxal = 2-oxopropanal
(R)-lactate = D-lactate

Other name(s):

glyoxylase III; GLO3

Systematic name:

(R)-lactate hydro-lyase

Comments:

The enzyme, described from the fungi Candida albicans and Schizosaccharomyces pombe, converts 2-oxopropanal to (R)-lactate in a single glutathione (GSH)-independent step. The other known route for this conversion is the two-step GSH-dependent pathway catalysed by EC 4.4.1.5 (lactoylglutathione lyase) and EC 3.1.2.6 (hydroxyacylglutathione hydrolase).

Links to other databases:

References:

1.	Hasim, S., Hussin, N.A., Alomar, F., Bidasee, K.R., Nickerson, K.W. and Wilson, M.A. A glutathione-independent glyoxalase of the DJ-1 superfamily plays an important role in managing metabolically generated methylglyoxal in Candida albicans. J. Biol. Chem. 289 (2014) 1662–1674. [DOI] [PMID: 24302734]
2.	Zhao, Q., Su, Y., Wang, Z., Chen, C., Wu, T. and Huang, Y. Identification of glutathione (GSH)-independent glyoxalase III from Schizosaccharomyces pombe. BMC Evol Biol 14:86 (2014). [DOI] [PMID: 24758716]

[EC 4.2.1.130 created 2011]

4.2.1.131

Accepted name:

carotenoid 1,2-hydratase

Reaction:

(1) 1-hydroxy-1,2-dihydrolycopene = lycopene + H₂O
(2) 1,1′-dihydroxy-1,1′,2,2′-tetrahydrolycopene = 1-hydroxy-1,2-dihydrolycopene + H₂O

For diagram of 4.2.1.131, click here and for diagram of mechanism, click here

Other name(s):

CrtC

Systematic name:

lycopene hydro-lyase (1-hydroxy-1,2-dihydrolycopene-forming)

Comments:

In Rubrivivax gelatinosus [1] and Thiocapsa roseopersicina [2] both products are formed, whereas Rhodobacter capsulatus [1] only gives 1-hydroxy-1,2-dihydrolycopene. Also acts on neurosporene giving 1-hydroxy-1,2-dihydroneurosporene with both organism but 1,1′-dihydroxy-1,1′,2,2′-tetrahydroneurosporene only with Rubrivivax gelatinosus.

Links to other databases:

References:

1.	Steiger, S., Mazet, A. and Sandmann, G. Heterologous expression, purification, and enzymatic characterization of the acyclic carotenoid 1,2-hydratase from Rubrivivax gelatinosus. Arch. Biochem. Biophys. 414 (2003) 51–58. [DOI] [PMID: 12745254]
2.	Hiseni, A., Arends, I.W. and Otten, L.G. Biochemical characterization of the carotenoid 1,2-hydratases (CrtC) from Rubrivivax gelatinosus and Thiocapsa roseopersicina. Appl. Microbiol. Biotechnol. 91 (2011) 1029–1036. [DOI] [PMID: 21590288]

[EC 4.2.1.131 created 2011]

4.2.2.25

Accepted name:

gellan lyase

Reaction:

Eliminative cleavage of β-D-glucopyranosyl-(1→4)-β-D-glucopyranosyluronate bonds of gellan backbone releasing tetrasaccharides containing a 4-deoxy-4,5-unsaturated D-glucopyranosyluronic acid at the non-reducing end. The tetrasaccharide produced from deacetylated gellan is β-D-4-deoxy-Δ⁴-GlcAp-(1→4)-β-D-Glcp-(1→4)-α-L-Rhap-(1→3)-β-D-Glcp.

Systematic name:

gellan β-D-glucopyranosyl-(1→4)-D-glucopyranosyluronate lyase

Comments:

The enzyme is highly specific to gellan, especially deacetylated gellan.

Links to other databases:

References:

1.	Hashimoto, W., Maesaka, K., Sato, N., Kimura, S., Yamamoto, K., Kumagai, H. and Murata, K. Microbial system for polysaccharide depolymerization: enzymatic route for gellan depolymerization by Bacillus sp. GL1. Arch. Biochem. Biophys. 339 (1997) 17–23. [DOI] [PMID: 9056228]
2.	Hashimoto, W., Sato, N., Kimura, S. and Murata, K. Polysaccharide lyase: molecular cloning of gellan lyase gene and formation of the lyase from a huge precursor protein in Bacillus sp. GL1. Arch. Biochem. Biophys. 354 (1998) 31–39. [DOI] [PMID: 9633595]
3.	Miyake, O., Kobayashi, E., Nankai, H., Hashimoto, W., Mikami, B. and Murata, K. Posttranslational processing of polysaccharide lyase: maturation route for gellan lyase in Bacillus sp. GL1. Arch. Biochem. Biophys. 422 (2004) 211–220. [DOI] [PMID: 14759609]

[EC 4.2.2.25 created 2011]

*EC

4.2.3.57

Accepted name:

(-)-β-caryophyllene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (-)-β-caryophyllene + diphosphate

For diagram of humulene-based sequiterpenoid biosynthesis, click here

Other name(s):

β-caryophyllene synthase; (2E,6E)-farnesyl-diphosphate diphosphate-lyase (caryophyllene-forming)

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase [(-)-β-caryophyllene-forming]

Comments:

Widely distributed in higher plants, cf. EC 4.2.3.89 (+)-β-caryophyllene synthase.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 110639-18-4

References:

1.	Cai, Y., Jia, J.W., Crock, J., Lin, Z.X., Chen, X.Y. and Croteau, R. A cDNA clone for β-caryophyllene synthase from Artemisia annua. Phytochemistry 61 (2002) 523–529. [DOI] [PMID: 12409018]

[EC 4.2.3.57 created 2011, modified 2011]

*EC

4.2.3.62

Accepted name:

(-)-γ-cadinene synthase [(2Z,6E)-farnesyl diphosphate cyclizing]

Reaction:

(2Z,6E)-farnesyl diphosphate = (-)-γ-cadinene + diphosphate

For diagram of ent-cadinane sesquiterpenoid biosynthesis, click here

Other name(s):

(-)-γ-cadinene cyclase

Systematic name:

(2Z,6E)-farnesyl-diphosphate diphosphate-lyase [(-)-γ-cadinene-forming]

Comments:

Isolated from the liverwort Heteroscyphus planus. cf EC 4.2.3.92 (+)-γ-cadinene synthase.

Links to other databases:

References:

1.	Nabeta, K., Fujita, M., Komuro, K., Katayama, K., and Takasawa, T. In vitro biosynthesis of cadinanes by cell-free extracts of cultured cells of Heteroscyphus planus. J. Chem. Soc., Perkin Trans. 1 (1997) 2065–2070.

[EC 4.2.3.62 created 2011, modified 2011]

4.2.3.78

Accepted name:

β-chamigrene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (+)-β-chamigrene + diphosphate

For diagram, click here

Systematic name:

(2E,6E)-farnesyl diphosphate lyase (cyclizing, (+)-β-chamigrene-forming)

Comments:

The recombinant enzyme from the plant Arabidopsis thaliana produces 27.3% (+)-α-barbatene, 17.8% (+)-thujopsene and 9.9% (+)-β-chamigrene [1] plus traces of other sesquiterpenoids [2]. See EC 4.2.3.69 (+)-α-barbatene synthase, and EC 4.2.3.79 thujopsene synthase.

Links to other databases:

References:

1.	Wu, S., Schoenbeck, M.A., Greenhagen, B.T., Takahashi, S., Lee, S., Coates, R.M. and Chappell, J. Surrogate splicing for functional analysis of sesquiterpene synthase genes. Plant Physiol. 138 (2005) 1322–1333. [DOI] [PMID: 15965019]
2.	Tholl, D., Chen, F., Petri, J., Gershenzon, J. and Pichersky, E. Two sesquiterpene synthases are responsible for the complex mixture of sesquiterpenes emitted from Arabidopsis flowers. Plant J. 42 (2005) 757–771. [DOI] [PMID: 15918888]

[EC 4.2.3.78 created 2011]

4.2.3.79

Accepted name:

thujopsene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (+)-thujopsene + diphosphate

For diagram, click here

Systematic name:

(2E,6E)-farnesyl diphosphate lyase (cyclizing, (+)-thujopsene-forming)

Comments:

Links to other databases:

References:

1.	Wu, S., Schoenbeck, M.A., Greenhagen, B.T., Takahashi, S., Lee, S., Coates, R.M. and Chappell, J. Surrogate splicing for functional analysis of sesquiterpene synthase genes. Plant Physiol. 138 (2005) 1322–1333. [DOI] [PMID: 15965019]
2.	Tholl, D., Chen, F., Petri, J., Gershenzon, J. and Pichersky, E. Two sesquiterpene synthases are responsible for the complex mixture of sesquiterpenes emitted from Arabidopsis flowers. Plant J. 42 (2005) 757–771. [DOI] [PMID: 15918888]

[EC 4.2.3.79 created 2011]

4.2.3.80

Accepted name:

α-longipinene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = α-longipinene + diphosphate

For diagram of humulene-based sequiterpenoid biosynthesis, click here and for mechanism, click here

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (α-longipinene-forming)

Comments:

The enzyme from Norway spruce produces longifolene as the main product (cf. EC 4.2.3.58, longifolene synthase). α-Longipinene constitutes about 15% of the total products.

Links to other databases:

References:

1.	Martin, D.M., Faldt, J. and Bohlmann, J. Functional characterization of nine Norway Spruce TPS genes and evolution of gymnosperm terpene synthases of the TPS-d subfamily. Plant Physiol. 135 (2004) 1908–1927. [DOI] [PMID: 15310829]
2.	Köpke, D., Schröder, R., Fischer, H.M., Gershenzon, J., Hilker, M. and Schmidt, A. Does egg deposition by herbivorous pine sawflies affect transcription of sesquiterpene synthases in pine? Planta 228 (2008) 427–438. [DOI] [PMID: 18493792]

[EC 4.2.3.80 created 2011]

4.2.3.81

Accepted name:

exo-α-bergamotene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (-)-exo-α-bergamotene + diphosphate

For diagram of santalene and bergamotene biosynthesis, click here

Glossary:

(-)-exo-α-bergamotene = (-)-trans-α-bergamotene = (1S,5S,6R)-2,6-dimethyl-6-(4-methylpent-3-en-1-yl)bicyclo[3.1.1]hept-2-ene

Other name(s):

trans-α-bergamotene synthase; LaBERS (gene name)

Systematic name:

(2E,6E)-farnesyl diphosphate lyase (cyclizing, (-)-exo-α-bergamotene-forming)

Comments:

The enzyme synthesizes a mixture of sesquiterpenoids from (2E,6E)-farnesyl diphosphate. As well as (-)-exo-α-bergamotene (74%) there were (E)-nerolidol (10%), (Z)-α-bisabolene (6%), (E)-β-farnesene (5%) and β-sesquiphellandrene (1%).

Links to other databases:

References:

1.	Schnee, C., Kollner, T.G., Held, M., Turlings, T.C., Gershenzon, J. and Degenhardt, J. The products of a single maize sesquiterpene synthase form a volatile defense signal that attracts natural enemies of maize herbivores. Proc. Natl. Acad. Sci. USA 103 (2006) 1129–1134. [DOI] [PMID: 16418295]
2.	Landmann, C., Fink, B., Festner, M., Dregus, M., Engel, K.H. and Schwab, W. Cloning and functional characterization of three terpene synthases from lavender (Lavandula angustifolia). Arch. Biochem. Biophys. 465 (2007) 417–429. [DOI] [PMID: 17662687]

[EC 4.2.3.81 created 2011]

4.2.3.82

Accepted name:

α-santalene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (+)-α-santalene + diphosphate

For diagram of santalene and bergamotene biosynthesis, click here

Glossary:

(-)-exo-α-bergamotene = (-)-trans-α-bergamotene = (1S,5S,6R)-2,6-dimethyl-6-(4-methylpent-3-en-1-yl)bicyclo[3.1.1]hept-2-ene

Systematic name:

(2E,6E)-farnesyl diphosphate lyase (cyclizing, (+)-α-santalene-forming)

Comments:

The enzyme synthesizes a mixture of sesquiterpenoids from (2E,6E)-farnesyl diphosphate. As well as (+)-α-santalene, (-)-β-santalene and (-)-exo-α-bergamotene are formed with traces of (+)-epi-β-santalene. See EC 4.2.3.83 [(-)-β-santalene synthase], and EC 4.2.3.81 [(-)-exo-α-bergamotene synthase]. cf. EC 4.2.3.50 α-santalene synthase [(2Z,6Z)-farnesyl diphosphate cyclizing]

Links to other databases:

References:

Jones, C.G., Moniodis, J., Zulak, K.G., Scaffidi, A., Plummer, J.A., Ghisalberti, E.L., Barbour, E.L. and Bohlmann, J. Sandalwood fragrance biosynthesis involves sesquiterpene synthases of both the terpene synthase (TPS)-a and TPS-b subfamilies, including santalene synthases. J. Biol. Chem. 286 (2011) 17445–17454. [DOI] [PMID: 21454632]

[EC 4.2.3.82 created 2011]

4.2.3.83

Accepted name:

β-santalene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (-)-β-santalene + diphosphate

For diagram of santalene and bergamotene biosynthesis, click here

Glossary:

(-)-exo-α-bergamotene = (-)-trans-α-bergamotene = (1S,5S,6R)-2,6-dimethyl-6-(4-methylpent-3-en-1-yl)bicyclo[3.1.1]hept-2-ene

Systematic name:

(2E,6E)-farnesyl diphosphate lyase (cyclizing, (-)-β-santalene-forming)

Comments:

The enzyme synthesizes a mixture of sesquiterpenoids from (2E,6E)-farnesyl diphosphate. As well as (-)-β-santalene (+)-α-santalene and (-)-exo-α-bergamotene are formed with traces of (+)-epi-β-santalene. See EC 4.2.3.82 [(+)-α-santalene synthase], and EC 4.2.3.81 [(-)-exo-α-bergamotene synthase].

Links to other databases:

References:

[EC 4.2.3.83 created 2011]

4.2.3.84

Accepted name:

10-epi-γ-eudesmol synthase

Reaction:

(2E,6E)-farnesyl diphosphate + H₂O = 10-epi-γ-eudesmol + diphosphate

For diagram of eudesmol and selinene biosynthesis, click here and for diagram of eudesmol biosynthesis, click here

Glossary:

10-epi-γ-eudesmol = 2-[(2R,4aS)-4a,8-dimethyl-1,2,3,4,4a,5,6,7-octahydronaphthalen-2-yl]propan-2-ol

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (10-epi-γ-eudesmol-forming)

Comments:

The recombinant enzyme from ginger (Zingiber zerumbet) gives 62.6% β-eudesmol, 16.8% 10-epi-γ-eudesmol, 10% α-eudesmol, and 5.6% aristolene. cf. EC 4.2.3.68 (β-eudesmol synthase) and EC 4.2.3.85 (α-eudesmol synthase)

Links to other databases:

References:

1.	Yu, F., Harada, H., Yamasaki, K., Okamoto, S., Hirase, S., Tanaka, Y., Misawa, N. and Utsumi, R. Isolation and functional characterization of a β-eudesmol synthase, a new sesquiterpene synthase from Zingiber zerumbet Smith. FEBS Lett. 582 (2008) 565–572. [DOI] [PMID: 18242187]

[EC 4.2.3.84 created 2011]

4.2.3.85

Accepted name:

α-eudesmol synthase

Reaction:

(2E,6E)-farnesyl diphosphate + H₂O = α-eudesmol + diphosphate

For diagram of eudesmol biosynthesis, click here

Glossary:

(-)-α-eudesmol = 2-[(2R,4aR,8aR)-4a,8-dimethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalen-2-yl]propan-2-ol

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (α-eudesmol-forming)

Comments:

Links to other databases:

References:

1.	Yu, F., Harada, H., Yamasaki, K., Okamoto, S., Hirase, S., Tanaka, Y., Misawa, N. and Utsumi, R. Isolation and functional characterization of a β-eudesmol synthase, a new sesquiterpene synthase from Zingiber zerumbet Smith. FEBS Lett. 582 (2008) 565–572. [DOI] [PMID: 18242187]

[EC 4.2.3.85 created 2011]

4.2.3.86

Accepted name:

7-epi-α-selinene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = 7-epi-α-selinene + diphosphate

For diagram of eudesmol and selinene biosynthesis, click here

Glossary:

7-epi-α-selinene = (2S,4aR,8aR)-4a,8-dimethyl-2-(prop-1-en-2-yl)-1,2,3,4,4a,5,6,8a-octahydronaphthalene

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (7-epi-α-selinene-forming)

Comments:

The recombinant enzyme from Vitis vinifera forms 49.5% (+)-valencene (cf. EC 4.2.3.73, valencene synthase) and 35.5% (-)-7-epi-α-selinene. Initial cyclization gives (+)-germacrene A in an enzyme bound form which is not released to the medium.

Links to other databases:

References:

1.	Lucker, J., Bowen, P. and Bohlmann, J. Vitis vinifera terpenoid cyclases: functional identification of two sesquiterpene synthase cDNAs encoding (+)-valencene synthase and (-)-germacrene D synthase and expression of mono- and sesquiterpene synthases in grapevine flowers and berries. Phytochemistry 65 (2004) 2649–2659. [DOI] [PMID: 15464152]
2.	Martin, D.M., Toub, O., Chiang, A., Lo, B.C., Ohse, S., Lund, S.T. and Bohlmann, J. The bouquet of grapevine (Vitis vinifera L. cv. Cabernet Sauvignon) flowers arises from the biosynthesis of sesquiterpene volatiles in pollen grains. Proc. Natl. Acad. Sci. USA 106 (2009) 7245–7250. [DOI] [PMID: 19359488]

[EC 4.2.3.86 created 2011]

4.2.3.87

Accepted name:

α-guaiene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = α-guaiene + diphosphate

For diagram of guaiene, α-gurjunene, patchoulol and viridiflorene biosynthesis, click here

Other name(s):

PatTps177 (gene name)

Systematic name:

(2Z,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, α-guaiene-forming)

Comments:

Requires Mg²⁺. The enzyme from Pogostemon cablin gives 13% α-guaiene as well as 37% (-)-patchoulol (see EC 4.2.3.70), 13% δ-guaiene (see EC 4.2.3.93), and traces of at least ten other sesquiterpenoids [1]. In Aquilaria crassna three clones of the enzyme gave about 80% δ-guaiene and 20% α-guaiene, with traces of α-humulene. A fourth clone gave 54% δ-guaiene and 45% α-guaiene [2].

Links to other databases:

References:

1.	Deguerry, F., Pastore, L., Wu, S., Clark, A., Chappell, J. and Schalk, M. The diverse sesquiterpene profile of patchouli, Pogostemon cablin, is correlated with a limited number of sesquiterpene synthases. Arch. Biochem. Biophys. 454 (2006) 123–136. [DOI] [PMID: 16970904]
2.	Kumeta, Y. and Ito, M. Characterization of δ-guaiene synthases from cultured cells of Aquilaria, responsible for the formation of the sesquiterpenes in agarwood. Plant Physiol. 154 (2010) 1998–2007. [DOI] [PMID: 20959422]

[EC 4.2.3.87 created 2011]

4.2.3.88

Accepted name:

viridiflorene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = viridiflorene + diphosphate

For diagram of guaiene, α-gurjunene, patchoulol and viridiflorene biosynthesis, click here

Other name(s):

TPS31

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (viridiflorene-forming)

Comments:

Viridiflorene is the only product of this enzyme from Solanum lycopersicum.

Links to other databases:

References:

Bleeker, P.M., Spyropoulou, E.A., Diergaarde, P.J., Volpin, H., De Both, M.T., Zerbe, P., Bohlmann, J., Falara, V., Matsuba, Y., Pichersky, E., Haring, M.A. and Schuurink, R.C. RNA-seq discovery, functional characterization, and comparison of sesquiterpene synthases from Solanum lycopersicum and Solanum habrochaites trichomes. Plant Mol. Biol. 77 (2011) 323–336. [DOI] [PMID: 21818683]

[EC 4.2.3.88 created 2011]

4.2.3.89

Accepted name:

(+)-β-caryophyllene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (+)-β-caryophyllene + diphosphate

For diagram of bicyclic and tricyclic sesquiterpenoids derived from humuladienyl cation, click here

Other name(s):

GcoA

Systematic name:

(2Z,6E)-farnesyl-diphosphate diphosphate-lyase [cyclizing, (+)-β-caryophyllene-forming]

Comments:

A multifunctional enzyme which also converts the (+)-β-caryophyllene to (+)-caryolan-1-ol (see EC 4.2.1.138, (+)-caryolan-1-ol synthase). cf. EC 4.2.3.57 (–)-β-caryophyllene synthase.

Links to other databases:

References:

1.	Nakano, C., Horinouchi, S. and Ohnishi, Y. Characterization of a novel sesquiterpene cyclase involved in (+)-caryolan-1-ol biosynthesis in Streptomyces griseus. J. Biol. Chem. 286 (2011) 27980–27987. [DOI] [PMID: 21693706]

[EC 4.2.3.89 created 2011]

4.2.3.90

Accepted name:

5-epi-α-selinene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = 5-epi-α-selinene + diphosphate

For diagram of eudesmol and selinene biosynthesis, click here

Glossary:

5-epi-α-selinene = 5β-eudesma-3,11-diene = (2R,4aR,8aS)-1,2,3,4,4a,5,6,8a-octahydro-4a,8-dimethyl-2-(prop-1-en-2-yl)naphthalene
[= 8a-epi-α-selinene which uses naththalene numbering not eudesmane]

Other name(s):

8a-epi-α-selinene synthase; NP1

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, 5-epi-α-selinene-forming)

Comments:

Requires Mg²⁺. The enzyme forms 5-epi-α-selinene possibly via germecrene A or a 1,6-hydride shift mechanism.

Links to other databases:

References:

1.	Agger, S.A., Lopez-Gallego, F., Hoye, T.R. and Schmidt-Dannert, C. Identification of sesquiterpene synthases from Nostoc punctiforme PCC 73102 and Nostoc sp. strain PCC 7120. J. Bacteriol. 190 (2008) 6084–6096. [DOI] [PMID: 18658271]

[EC 4.2.3.90 created 2011]

4.2.3.91

Accepted name:

cubebol synthase

Reaction:

(2E,6E)-farnesyl diphosphate + H₂O = cubebol + diphosphate

For diagram of cadinane sesquiterpenoid biosynthesis, click here and for diagram of cadinene, cubebol and muuroladiene biosynthesis, click here

Other name(s):

Cop4

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, cubebol-forming)

Comments:

Requires Mg²⁺. The enzyme gives 28% cubebol, 29% (-)-germacrene D, 10% (+)-δ-cadinene and traces of several other sesquiterpenoids. See also EC 4.2.3.75 (–)-germacrene D synthase and EC 4.2.3.13 (+)-δ-cadinene synthase.

Links to other databases:

References:

1.	Lopez-Gallego, F., Agger, S.A., Abate-Pella, D., Distefano, M.D. and Schmidt-Dannert, C. Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: catalytic promiscuity and cyclization of farnesyl pyrophosphate geometric isomers. ChemBioChem 11 (2010) 1093–1106. [DOI] [PMID: 20419721]

[EC 4.2.3.91 created 2011]

4.2.3.92

Accepted name:

(+)-γ-cadinene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (+)-γ-cadinene + diphosphate

For diagram of cadinane sesquiterpenoid biosynthesis, click here and for diagram of cadinene, cubebol and muuroladiene biosynthesis, click here

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase [(+)-γ-cadinene-forming]

Comments:

The cloned enzyme from the melon, Cucumis melo, gave mainly δ- and γ-cadinene with traces of several other sesquiterpenoids cf. EC 4.2.3.62 (-)-γ-cadinene synthase [(2Z,6E)-farnesyl diphosphate cyclizing]; EC 4.2.3.13 (+)-δ-cadinene synthase.

Links to other databases:

References:

1.	Iijima, Y., Davidovich-Rikanati, R., Fridman, E., Gang, D.R., Bar, E., Lewinsohn, E. and Pichersky, E. The biochemical and molecular basis for the divergent patterns in the biosynthesis of terpenes and phenylpropenes in the peltate glands of three cultivars of basil. Plant Physiol. 136 (2004) 3724–3736. [DOI] [PMID: 15516500]
2.	Portnoy, V., Benyamini, Y., Bar, E., Harel-Beja, R., Gepstein, S., Giovannoni, J.J., Schaffer, A.A., Burger, J., Tadmor, Y., Lewinsohn, E. and Katzir, N. The molecular and biochemical basis for varietal variation in sesquiterpene content in melon (Cucumis melo L.) rinds. Plant Mol. Biol. 66 (2008) 647–661. [DOI] [PMID: 18264780]

[EC 4.2.3.92 created 2011]

4.2.3.93

Accepted name:

δ-guaiene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = δ-guaiene + diphosphate

For diagram of guaiene, α-gurjunene, patchoulol and viridiflorene biosynthesis, click here

Glossary:

δ-guaiene = α-bulnesene

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, δ-guaiene-forming)

Comments:

Requires Mg²⁺. In Aquilaria crassna three clones of the enzyme gave about 80% δ-guaiene and 20% α-guaiene (see also EC 4.2.3.87). A fourth clone gave 54% δ-guaiene and 45% α-guaiene [2]. The enzyme from Pogostemon cablin gives 13% δ-guaiene as well as 37% (-)-patchoulol (see EC 4.2.3.70), 13% α-guaiene (see EC 4.2.3.87), and traces of at least ten other sesquiterpenoids [1].

Links to other databases:

References:

1.	Deguerry, F., Pastore, L., Wu, S., Clark, A., Chappell, J. and Schalk, M. The diverse sesquiterpene profile of patchouli, Pogostemon cablin, is correlated with a limited number of sesquiterpene synthases. Arch. Biochem. Biophys. 454 (2006) 123–136. [DOI] [PMID: 16970904]
2.	Kumeta, Y. and Ito, M. Characterization of δ-guaiene synthases from cultured cells of Aquilaria, responsible for the formation of the sesquiterpenes in agarwood. Plant Physiol. 154 (2010) 1998–2007. [DOI] [PMID: 20959422]

[EC 4.2.3.93 created 2011]

4.3.3.6

Accepted name:

pyridoxal 5′-phosphate synthase (glutamine hydrolysing)

Reaction:

D-ribose 5-phosphate + D-glyceraldehyde 3-phosphate + L-glutamine = pyridoxal 5′-phosphate + L-glutamate + 3 H₂O + phosphate (overall reaction)
(1a) L-glutamine + H₂O = L-glutamate + NH₃
(1b) D-ribose 5-phosphate + D-glyceraldehyde 3-phosphate + NH₃ = pyridoxal 5′-phosphate + 4 H₂O + phosphate

Other name(s):

PdxST

Systematic name:

D-ribose 5-phosphate,D-glyceraldehyde 3-phosphate pyridoxal 5′-phosphate-lyase

Comments:

The ammonia is provided by the glutaminase subunit and channeled to the active site of the lyase subunit by a 100 Å tunnel. The enzyme can also use ribulose 5-phosphate and dihydroxyacetone phosphate. The enzyme complex is found in aerobic bacteria, archaea, fungi and plants.

Links to other databases:

References:

1.	Burns, K.E., Xiang, Y., Kinsland, C.L., McLafferty, F.W. and Begley, T.P. Reconstitution and biochemical characterization of a new pyridoxal-5′-phosphate biosynthetic pathway. J. Am. Chem. Soc. 127 (2005) 3682–3683. [DOI] [PMID: 15771487]
2.	Raschle, T., Amrhein, N. and Fitzpatrick, T.B. On the two components of pyridoxal 5′-phosphate synthase from Bacillus subtilis. J. Biol. Chem. 280 (2005) 32291–32300. [DOI] [PMID: 16030023]
3.	Strohmeier, M., Raschle, T., Mazurkiewicz, J., Rippe, K., Sinning, I., Fitzpatrick, T.B. and Tews, I. Structure of a bacterial pyridoxal 5′-phosphate synthase complex. Proc. Natl. Acad. Sci. USA 103 (2006) 19284–19289. [DOI] [PMID: 17159152]
4.	Raschle, T., Arigoni, D., Brunisholz, R., Rechsteiner, H., Amrhein, N. and Fitzpatrick, T.B. Reaction mechanism of pyridoxal 5′-phosphate synthase. Detection of an enzyme-bound chromophoric intermediate. J. Biol. Chem. 282 (2007) 6098–6105. [DOI] [PMID: 17189272]
5.	Hanes, J.W., Keresztes, I. and Begley, T.P. Trapping of a chromophoric intermediate in the Pdx1-catalyzed biosynthesis of pyridoxal 5′-phosphate. Angew. Chem. Int. Ed. Engl. 47 (2008) 2102–2105. [DOI] [PMID: 18260082]
6.	Hanes, J.W., Burns, K.E., Hilmey, D.G., Chatterjee, A., Dorrestein, P.C. and Begley, T.P. Mechanistic studies on pyridoxal phosphate synthase: the reaction pathway leading to a chromophoric intermediate. J. Am. Chem. Soc. 130 (2008) 3043–3052. [DOI] [PMID: 18271580]
7.	Hanes, J.W., Keresztes, I. and Begley, T.P. ¹³C NMR snapshots of the complex reaction coordinate of pyridoxal phosphate synthase. Nat. Chem. Biol. 4 (2008) 425–430. [DOI] [PMID: 18516049]
8.	Wallner, S., Neuwirth, M., Flicker, K., Tews, I. and Macheroux, P. Dissection of contributions from invariant amino acids to complex formation and catalysis in the heteromeric pyridoxal 5-phosphate synthase complex from Bacillus subtilis. Biochemistry 48 (2009) 1928–1935. [DOI] [PMID: 19152323]

[EC 4.3.3.6 created 2011]

5.1.3.24

Accepted name:

N-acetylneuraminate epimerase

Reaction:

N-acetyl-α-neuraminate = N-acetyl-β-neuraminate (oveall reaction)
(1a) N-acetyl-α-neuraminate = aceneuramate
(1b) aceneuramate = N-acetyl-β-neuraminate

Glossary:

aceneuramate = (4S,5R,6R,7S,8R)-5-acetamido-4,6,7,8,9-pentahydroxy-2-oxononanoate

Other name(s):

sialic acid epimerase; N-acetylneuraminate mutarotase; NanM; NanQ

Systematic name:

N-acetyl-α-neuraminate 2-epimerase

Comments:

Sialoglycoconjugates present in vertebrates are linked exclusively by α-linkages and are released in α form during degradation. This enzyme accelerates maturotation to the β form via the open form (which also occurs as a slow spontaneous reaction). The open form is necessary for further metabolism by the bacteria.

Links to other databases:

References:

1.	Severi, E., Müller, A., Potts, J.R., Leech, A., Williamson, D., Wilson, K.S. and Thomas, G.H. Sialic acid mutarotation is catalyzed by the Escherichia coli β-propeller protein YjhT. J. Biol. Chem. 283 (2008) 4841–4849. [DOI] [PMID: 18063573]
2.	Kentache, T., Thabault, L., Deumer, G., Haufroid, V., Frederick, R., Linster, C.L., Peracchi, A., Veiga-da-Cunha, M., Bommer, G.T. and Van Schaftingen, E. The metalloprotein YhcH is an anomerase providing N-acetylneuraminate aldolase with the open form of its substrate. J. Biol. Chem. :100699 (2021). [DOI] [PMID: 33895133]

[EC 5.1.3.24 created 2011, modified 2021]

5.2.1.3

Deleted entry:

retinal isomerase. Now known to be catalysed by a pathway involving EC 1.1.1.300, NADP-retinol dehydrogenase; EC 2.3.1.135, phosphatidylcholine—retinol O-acyltransferase; EC 3.1.1.64, retinoid isomerohydrolase; and EC 1.1.1.315, 11-cis-retinol dehydrogenase.

[EC 5.2.1.3 created 1961, modified 1976, deleted 2011]

5.2.1.7

Transferred entry:

retinol isomerase. Transferred to EC 3.1.1.64, retinoid isomerohydrolase.

[EC 5.2.1.7 created 1989, deleted 2011]

5.3.2.3

Accepted name:

TDP-4-oxo-6-deoxy-α-D-glucose-3,4-oxoisomerase (dTDP-3-dehydro-6-deoxy-α-D-galactopyranose-forming)

Reaction:

dTDP-4-dehydro-6-deoxy-α-D-glucopyranose = dTDP-3-dehydro-6-deoxy-α-D-galactopyranose

For diagram of dTDP-Fuc3NAc and dTDP-Fuc4NAc biosynthesis, click here

Other name(s):

dTDP-6-deoxy-hex-4-ulose isomerase; TDP-6-deoxy-hex-4-ulose isomerase; FdtA

Systematic name:

dTDP-4-dehydro-6-deoxy-α-D-glucopyranose:dTDP-3-dehydro-6-deoxy-α-D-galactopyranose isomerase

Comments:

The enzyme is involved in the biosynthesis of dTDP-3-acetamido-3,6-dideoxy-α-D-galactose. Four moieties of α-D-rhamnose and two moities of 3-acetamido-3,6-dideoxy-α-D-galactose form the repeating unit of the glycan chain in the S-layer of the bacterium Aneurinibacillus thermoaerophilus.

Links to other databases:

References:

1.	Pfoestl, A., Hofinger, A., Kosma, P. and Messner, P. Biosynthesis of dTDP-3-acetamido-3,6-dideoxy-α-D-galactose in Aneurinibacillus thermoaerophilus L420-91^T. J. Biol. Chem. 278 (2003) 26410–26417. [DOI] [PMID: 12740380]
2.	Davis, M.L., Thoden, J.B. and Holden, H.M. The x-ray structure of dTDP-4-keto-6-deoxy-D-glucose-3,4-ketoisomerase. J. Biol. Chem. 282 (2007) 19227–19236. [DOI] [PMID: 17459872]

[EC 5.3.2.3 created 2011]

5.3.2.4

Accepted name:

TDP-4-oxo-6-deoxy-α-D-glucose-3,4-oxoisomerase (dTDP-3-dehydro-6-deoxy-α-D-glucopyranose-forming)

Reaction:

dTDP-4-dehydro-6-deoxy-α-D-glucopyranose = dTDP-3-dehydro-6-deoxy-α-D-glucopyranose

For diagram of dTDP-D-mycaminose biosynthesis, click here

Other name(s):

TDP-4-keto-6-deoxy-D-glucose-3,4-ketoisomerase (ambiguous); Tyl1a; dTDP-4-keto-6-deoxy-D-glucose-3,4-ketoisomerase (ambiguous)

Systematic name:

dTDP-4-dehydro-6-deoxy-α-D-glucopyranose:dTDP-3-dehydro-6-deoxy-α-D-glucopyranose isomerase

Comments:

The enzyme is involved in biosynthesis of D-mycaminose.

Links to other databases:

References:

[EC 5.3.2.4 created 2011]

*EC

5.3.3.16

Transferred entry:

4-oxalomesaconate tautomerase. Now EC 5.3.2.8, 4-oxalomesaconate tautomerase

[EC 5.3.3.16 created 2011, modified 2011, deleted 2013]

5.3.3.18

Accepted name:

2-(1,2-epoxy-1,2-dihydrophenyl)acetyl-CoA isomerase

Reaction:

2-(1,2-epoxy-1,2-dihydrophenyl)acetyl-CoA = 2-oxepin-2(3H)-ylideneacetyl-CoA

For diagram of aerobic phenylacetate catabolism, click here

Glossary:

2-(1,2-epoxy-1,2-dihydrophenyl)acetyl-CoA = 2-{7-oxabicyclo[4.1.0]hepta-2,4-dien-1-yl}acetyl-CoA
oxepin-CoA = 2-oxepin-2(3H)-ylideneacetyl-CoA

Other name(s):

paaG (gene name); 1,2-epoxyphenylacetyl-CoA isomerase (misleading)

Systematic name:

2-(1,2-epoxy-1,2-dihydrophenyl)acetyl-CoA isomerase

Comments:

The enzyme catalyses the reversible isomerization of 2-(1,2-epoxy-1,2-dihydrophenyl)acetyl-CoA to the unusual unsaturated, oxygen-containing, seven-member heterocyclic enol ether 2-oxepin-2(3H)-ylideneacetyl-CoA, as part of an aerobic phenylacetate degradation pathway.

Links to other databases:

References:

1.	Ismail, W., El-Said Mohamed, M., Wanner, B.L., Datsenko, K.A., Eisenreich, W., Rohdich, F., Bacher, A. and Fuchs, G. Functional genomics by NMR spectroscopy. Phenylacetate catabolism in Escherichia coli. Eur. J. Biochem. 270 (2003) 3047–3054. [DOI] [PMID: 12846838]
2.	Teufel, R., Mascaraque, V., Ismail, W., Voss, M., Perera, J., Eisenreich, W., Haehnel, W. and Fuchs, G. Bacterial phenylalanine and phenylacetate catabolic pathway revealed. Proc. Natl. Acad. Sci. USA 107 (2010) 14390–14395. [DOI] [PMID: 20660314]

[EC 5.3.3.18 created 2011]

5.4.4.5

Accepted name:

9,12-octadecadienoate 8-hydroperoxide 8R-isomerase

Reaction:

(8R,9Z,12Z)-8-hydroperoxyoctadeca-9,12-dienoate = (5S,8R,9Z,12Z)-5,8-dihydroxyoctadeca-9,12-dienoate

Other name(s):

5,8-LDS (bifunctional enzyme); 5,8-linoleate diol synthase (bifunctional enzyme); 8-hydroperoxide isomerase; (8R,9Z,12Z)-8-hydroperoxy-9,12-octadecadienoate mutase ((5S,8R,9Z,12Z)-5,8-dihydroxy-9,12-octadecadienoate-forming); PpoA

Systematic name:

(8R,9Z,12Z)-8-hydroperoxyoctadeca-9,12-dienoate hydroxymutase [(5S,8R,9Z,12Z)-5,8-dihydroxyoctadeca-9,12-dienoate-forming]

Comments:

The enzyme contains heme [3]. The bifunctional enzyme from Aspergillus nidulans uses different heme domains to catalyse two separate reactions. Linoleic acid is oxidized within the N-terminal heme peroxidase domain to (8R,9Z,12Z)-8-hydroperoxyoctadeca-9,12-dienoate (cf. EC 1.13.11.60, linoleate 8R-lipoxygenase), which is subsequently isomerized to (5S,8R,9Z,12Z)-5,8-dihydroxyoctadeca-9,12-dienoate within the C-terminal P-450 heme thiolate domain [3].

Links to other databases:

References:

1.	Hoffmann, I., Jerneren, F., Garscha, U. and Oliw, E.H. Expression of 5,8-LDS of Aspergillus fumigatus and its dioxygenase domain. A comparison with 7,8-LDS, 10-dioxygenase, and cyclooxygenase. Arch. Biochem. Biophys. 506 (2011) 216–222. [DOI] [PMID: 21130068]
2.	Jerneren, F., Garscha, U., Hoffmann, I., Hamberg, M. and Oliw, E.H. Reaction mechanism of 5,8-linoleate diol synthase, 10R-dioxygenase, and 8,11-hydroperoxide isomerase of Aspergillus clavatus. Biochim. Biophys. Acta 1801 (2010) 503–507. [DOI] [PMID: 20045744]
3.	Brodhun, F., Gobel, C., Hornung, E. and Feussner, I. Identification of PpoA from Aspergillus nidulans as a fusion protein of a fatty acid heme dioxygenase/peroxidase and a cytochrome P₄₅₀. J. Biol. Chem. 284 (2009) 11792–11805. [DOI] [PMID: 19286665]

[EC 5.4.4.5 created 2011]

5.4.4.6

Accepted name:

9,12-octadecadienoate 8-hydroperoxide 8S-isomerase

Reaction:

(8R,9Z,12Z)-8-hydroperoxyoctadeca-9,12-dienoate = (7S,8S,9Z,12Z)-7,8-dihydroxyoctadeca-9,12-dienoate

Other name(s):

8-hydroperoxide isomerase (ambiguous); (8R,9Z,12Z)-8-hydroperoxy-9,12-octadecadienoate mutase ((7S,8S,9Z,12Z)-7,8-dihydroxy-9,12-octadecadienoate-forming)

Systematic name:

(8R,9Z,12Z)-8-hydroperoxyoctadeca-9,12-dienoate hydroxymutase [(7S,8S,9Z,12Z)-7,8-dihydroxyoctadeca-9,12-dienoate-forming]

Comments:

The enzyme contains heme. The bifunctional enzyme from Gaeumannomyces graminis catalyses the oxidation of linoleic acid to (8R,9Z,12Z)-8-hydroperoxyoctadeca-9,12-dienoate (cf. EC 1.13.11.60, linoleate 8R-lipoxygenase), which is then isomerized to (7S,8S,9Z,12Z)-5,8-dihydroxyoctadeca-9,12-dienoate [3].

Links to other databases:

References:

1.	Hamberg, M., Zhang, L.-Y., Brodowsky, I.D. and Oliw, E.H. Sequential oxygenation of linoleic acid in the fungus Gaeumannomyces graminis: stereochemistry of dioxygenase and hydroperoxide isomerase reactions. Arch. Biochem. Biophys. 309 (1994) 77–80. [DOI] [PMID: 8117115]
2.	Su, C., Sahlin, M. and Oliw, E.H. A protein radical and ferryl intermediates are generated by linoleate diol synthase, a ferric hemeprotein with dioxygenase and hydroperoxide isomerase activities. J. Biol. Chem. 273 (1998) 20744–20751. [DOI] [PMID: 9694817]
3.	Su, C. and Oliw, E.H. Purification and characterization of linoleate 8-dioxygenase from the fungus Gaeumannomyces graminis as a novel hemoprotein. J. Biol. Chem. 271 (1996) 14112–14118. [DOI] [PMID: 8662736]

[EC 5.4.4.6 created 2011]

*EC

5.4.99.25

Accepted name:

tRNA pseudouridine⁵⁵ synthase

Reaction:

tRNA uridine⁵⁵ = tRNA pseudouridine⁵⁵

Other name(s):

TruB; aCbf5; Pus4; YNL292w (gene name); Ψ⁵⁵ tRNA pseudouridine synthase; tRNA:Ψ⁵⁵-synthase; tRNA pseudouridine 55 synthase; tRNA:pseudouridine-55 synthase; Ψ⁵⁵ synthase; tRNA Ψ⁵⁵ synthase; tRNA:Ψ⁵⁵ synthase; tRNA-uridine⁵⁵ uracil mutase; Pus10; tRNA-uridine^54/55 uracil mutase

Systematic name:

tRNA-uridine⁵⁵ uracil mutase

Comments:

Pseudouridine synthase TruB from Escherichia coli specifically modifies uridine⁵⁵ in tRNA molecules [1]. The bifunctional archaeal enzyme also catalyses the pseudouridylation of uridine⁵⁴ [6]. It is not known whether the enzyme from Escherichia coli can also act on position 54 in vitro, since this position is occupied in Escherichia coli tRNAs by thymine.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 430429-15-5

References:

1.	Nurse, K., Wrzesinski, J., Bakin, A., Lane, B.G. and Ofengand, J. Purification, cloning, and properties of the tRNA Ψ⁵⁵ synthase from Escherichia coli. RNA 1 (1995) 102–112. [PMID: 7489483]
2.	Becker, H.F., Motorin, Y., Planta, R.J. and Grosjean, H. The yeast gene YNL292w encodes a pseudouridine synthase (Pus4) catalyzing the formation of Ψ⁵⁵ in both mitochondrial and cytoplasmic tRNAs. Nucleic Acids Res. 25 (1997) 4493–4499. [DOI] [PMID: 9358157]
3.	Pienkowska, J., Wrzesinski, J. and Szweykowska-Kulinska, Z. A cell-free yellow lupin extract containing activities of pseudouridine 35 and 55 synthases. Acta Biochim. Pol. 45 (1998) 745–754. [PMID: 9918501]
4.	Chaudhuri, B.N., Chan, S., Perry, L.J. and Yeates, T.O. Crystal structure of the apo forms of Ψ55 tRNA pseudouridine synthase from Mycobacterium tuberculosis: a hinge at the base of the catalytic cleft. J. Biol. Chem. 279 (2004) 24585–24591. [DOI] [PMID: 15028724]
5.	Hoang, C., Hamilton, C.S., Mueller, E.G. and Ferre-D'Amare, A.R. Precursor complex structure of pseudouridine synthase TruB suggests coupling of active site perturbations to an RNA-sequestering peripheral protein domain. Protein Sci. 14 (2005) 2201–2206. [DOI] [PMID: 15987897]
6.	Gurha, P. and Gupta, R. Archaeal Pus10 proteins can produce both pseudouridine 54 and 55 in tRNA. RNA 14 (2008) 2521–2527. [DOI] [PMID: 18952823]

[EC 5.4.99.25 created 2011, modified 2011]

5.4.99.42

Accepted name:

tRNA pseudouridine³¹ synthase

Reaction:

tRNA uridine³¹ = tRNA pseudouridine³¹

Other name(s):

Pus6p

Systematic name:

tRNA-uridine³¹ uracil mutase

Comments:

The enzyme specifically acts on uridine³¹ in tRNA.

Links to other databases:

References:

1.	Ansmant, I., Motorin, Y., Massenet, S., Grosjean, H. and Branlant, C. Identification and characterization of the tRNA:Ψ³¹-synthase (Pus6p) of Saccharomyces cerevisiae. J. Biol. Chem. 276 (2001) 34934–34940. [DOI] [PMID: 11406626]

[EC 5.4.99.42 created 2011]

5.4.99.43

Accepted name:

21S rRNA pseudouridine²⁸¹⁹ synthase

Reaction:

21S rRNA uridine²⁸¹⁹ = 21S rRNA pseudouridine²⁸¹⁹

Other name(s):

Pus5p

Systematic name:

21S rRNA-uridine²⁸¹⁹ uracil mutase

Comments:

The enzyme specifically acts on uridine²⁸¹⁹ in 21S rRNA.

Links to other databases:

References:

1.	Ansmant, I., Massenet, S., Grosjean, H., Motorin, Y. and Branlant, C. Identification of the Saccharomyces cerevisiae RNA:pseudouridine synthase responsible for formation of Ψ²⁸¹⁹ in 21S mitochondrial ribosomal RNA. Nucleic Acids Res. 28 (2000) 1941–1946. [DOI] [PMID: 10756195]

[EC 5.4.99.43 created 2011]

5.4.99.44

Accepted name:

mitochondrial tRNA pseudouridine^27/28 synthase

Reaction:

mitochondrial tRNA uridine^27/28 = mitochondrial tRNA pseudouridine^27/28

Other name(s):

Pus2; Pus2p; RNA:pseudouridine synthases 2

Systematic name:

mitochondrial tRNA-uridine^27/28 uracil mutase

Comments:

The mitochondrial enzyme Pus2p is specific for position 27 or 28 in mitochondrial tRNA [1].

Links to other databases:

References:

1.	Behm-Ansmant, I., Branlant, C. and Motorin, Y. The Saccharomyces cerevisiae Pus2 protein encoded by YGL063w ORF is a mitochondrial tRNA:Ψ^27/28-synthase. RNA 13 (2007) 1641–1647. [DOI] [PMID: 17684231]

[EC 5.4.99.44 created 2011]

5.4.99.45

Accepted name:

tRNA pseudouridine^38/39 synthase

Reaction:

tRNA uridine^38/39 = tRNA pseudouridine^38/39

Other name(s):

Deg1; Pus3p; pseudouridine synthase 3

Systematic name:

tRNA-uridine^38/39 uracil mutase

Comments:

The enzyme from Saccharomyces cerevisiae is active only towards uridine³⁸ and uridine³⁹, and shows no activity with uridine⁴⁰ (cf. EC 5.4.99.12, tRNA pseudouridine^38-40 synthase) [1]. In vitro the enzyme from mouse is active on uridine³⁹ and very slightly on uridine³⁸ (human tRNA^Leu) [2].

Links to other databases:

References:

1.	Lecointe, F., Simos, G., Sauer, A., Hurt, E.C., Motorin, Y. and Grosjean, H. Characterization of yeast protein Deg1 as pseudouridine synthase (Pus3) catalyzing the formation of Ψ³⁸ and Ψ³⁹ in tRNA anticodon loop. J. Biol. Chem. 273 (1998) 1316–1323. [DOI] [PMID: 9430663]
2.	Chen, J. and Patton, J.R. Pseudouridine synthase 3 from mouse modifies the anticodon loop of tRNA. Biochemistry 39 (2000) 12723–12730. [DOI] [PMID: 11027153]

[EC 5.4.99.45 created 2011]

5.4.99.46

Accepted name:

shionone synthase

Reaction:

(3S)-2,3-epoxy-2,3-dihydrosqualene = shionone

For diagram of baccharis oxide, baruol and shionone biosynthesis, click here

Systematic name:

(3S)-2,3-epoxy-2,3-dihydrosqualene mutase (cyclizing, shionone-forming)

Comments:

The enzyme gives traces of four other triterpenoids

Links to other databases:

References:

1.	Sawai, S., Uchiyama, H., Mizuno, S., Aoki, T., Akashi, T., Ayabe, S. and Takahashi, T. Molecular characterization of an oxidosqualene cyclase that yields shionone, a unique tetracyclic triterpene ketone of Aster tataricus. FEBS Lett. 585 (2011) 1031–1036. [DOI] [PMID: 21377465]

[EC 5.4.99.46 created 2011]

5.4.99.47

Accepted name:

parkeol synthase

Reaction:

(3S)-2,3-epoxy-2,3-dihydrosqualene = parkeol

For diagram of cucurbitadienol, cycloartenol, lanosterol and prostadienol biosynthesis, click here

Systematic name:

(3S)-2,3-epoxy-2,3-dihydrosqualene mutase (cyclizing, parkeol-forming)

Comments:

The enzyme from rice (Oryza sativa) produces parkeol as a single product [1].

Links to other databases:

References:

1.	Ito, R., Mori, K., Hashimoto, I., Nakano, C., Sato, T. and Hoshino, T. Triterpene cyclases from Oryza sativa L.: cycloartenol, parkeol and achilleol B synthases. Org. Lett. 13 (2011) 2678–2681. [DOI] [PMID: 21526825]

[EC 5.4.99.47 created 2011]

5.4.99.48

Accepted name:

achilleol B synthase

Reaction:

(3S)-2,3-epoxy-2,3-dihydrosqualene = achilleol B

For diagram of beta-amyrin and soysapogenol biosynthesis, click here

Systematic name:

(3S)-2,3-epoxy-2,3-dihydrosqualene mutase (cyclizing, achilleol-B-forming)

Comments:

Achilleol B is probably formed by cleavage of the 8-14 and 9-10 bonds of (3S)-2,3-epoxy-2,3-dihydrosqualene as part of the cyclization reaction, after formation of the oleanane skeleton.

Links to other databases:

References:

1.	Ito, R., Mori, K., Hashimoto, I., Nakano, C., Sato, T. and Hoshino, T. Triterpene cyclases from Oryza sativa L.: cycloartenol, parkeol and achilleol B synthases. Org. Lett. 13 (2011) 2678–2681. [DOI] [PMID: 21526825]

[EC 5.4.99.48 created 2011]

5.4.99.49

Accepted name:

glutinol synthase

Reaction:

(3S)-2,3-epoxy-2,3-dihydrosqualene = glutinol

For diagram of friedelin, glutinol, isomultiflorenol and taraxerol biosynthesis, click here

Systematic name:

(3S)-2,3-epoxy-2,3-dihydrosqualene mutase (cyclizing, glutinol-forming)

Comments:

The enzyme from Kalanchoe daigremontiana also gives traces of other triterpenoids.

Links to other databases:

References:

1.	Wang, Z., Yeats, T., Han, H. and Jetter, R. Cloning and characterization of oxidosqualene cyclases from Kalanchoe daigremontiana: enzymes catalyzing up to 10 rearrangement steps yielding friedelin and other triterpenoids. J. Biol. Chem. 285 (2010) 29703–29712. [DOI] [PMID: 20610397]

[EC 5.4.99.49 created 2011]

5.4.99.50

Accepted name:

friedelin synthase

Reaction:

(3S)-2,3-epoxy-2,3-dihydrosqualene = friedelin

For diagram of friedelin, glutinol, isomultiflorenol and taraxerol biosynthesis, click here

Systematic name:

(3S)-2,3-epoxy-2,3-dihydrosqualene mutase (cyclizing, friedelin-forming)

Comments:

The enzyme from Kalanchoe daigremontiana also gives traces of other triterpenoids.

Links to other databases:

References:

1.	Wang, Z., Yeats, T., Han, H. and Jetter, R. Cloning and characterization of oxidosqualene cyclases from Kalanchoe daigremontiana: enzymes catalyzing up to 10 rearrangement steps yielding friedelin and other triterpenoids. J. Biol. Chem. 285 (2010) 29703–29712. [DOI] [PMID: 20610397]

[EC 5.4.99.50 created 2011]

5.4.99.51

Accepted name:

baccharis oxide synthase

Reaction:

(3S)-2,3-epoxy-2,3-dihydrosqualene = baccharis oxide

For diagram of baccharis oxide, baruol and shionone biosynthesis, click here

Systematic name:

(3S)-2,3-epoxy-2,3-dihydrosqualene mutase (cyclizing, baccharis-oxide-forming)

Comments:

The enzyme from Stevia rebaudiana also gives traces of other triterpenoids.

Links to other databases:

References:

1.	Shibuya, M., Sagara, A., Saitoh, A., Kushiro, T. and Ebizuka, Y. Biosynthesis of baccharis oxide, a triterpene with a 3,10-oxide bridge in the A-ring. Org. Lett. 10 (2008) 5071–5074. [DOI] [PMID: 18850716]

[EC 5.4.99.51 created 2011]

5.4.99.52

Accepted name:

α-seco-amyrin synthase

Reaction:

(3S)-2,3-epoxy-2,3-dihydrosqualene = α-seco-amyrin

For diagram of α-amyrin, α-seco-amyrin and germanicol biosynthesis, click here

Glossary:

α-seco-amyrin = 8,14-secoursa-7,13-diene-3β-ol

Systematic name:

(3S)-2,3-epoxy-2,3-dihydrosqualene mutase (cyclizing, α-seco-amyrin-forming)

Comments:

The enzyme from Arabidopsis thaliana is multifunctional and produces about equal amounts of α- and β-seco-amyrin. See EC 5.4.99.54, β-seco-amyrin synthase.

Links to other databases:

References:

1.	Shibuya, M., Xiang, T., Katsube, Y., Otsuka, M., Zhang, H. and Ebizuka, Y. Origin of structural diversity in natural triterpenes: direct synthesis of seco-triterpene skeletons by oxidosqualene cyclase. J. Am. Chem. Soc. 129 (2007) 1450–1455. [DOI] [PMID: 17263431]

[EC 5.4.99.52 created 2011]

5.4.99.53

Accepted name:

marneral synthase

Reaction:

(3S)-2,3-epoxy-2,3-dihydrosqualene = marneral

For diagram of arabidiol, camellidiol and thalianol biosynthesis, click here

Systematic name:

(3S)-2,3-epoxy-2,3-dihydrosqualene mutase (cyclizing, marneral-forming)

Comments:

Marneral is a triterpenoid formed by Grob fragmentation of the A ring of 2,3-epoxy-2,3-dihydrosqualene during cyclization.

Links to other databases:

References:

1.	Xiong, Q., Wilson, W.K. and Matsuda, S.P.T. An Arabidopsis oxidosqualene cyclase catalyzes iridal skeleton formation by Grob fragmentation. Angew. Chem. Int. Ed. Engl. 45 (2006) 1285–1288. [DOI] [PMID: 16425307]

[EC 5.4.99.53 created 2011]

5.4.99.54

Accepted name:

β-seco-amyrin synthase

Reaction:

(3S)-2,3-epoxy-2,3-dihydrosqualene = β-seco-amyrin

For diagram of beta-amyrin and soysapogenol biosynthesis, click here

Glossary:

β-seco-amyrin = 8,14-secooleana-7,13-diene-3β-ol

Systematic name:

(3S)-2,3-epoxy-2,3-dihydrosqualene mutase (cyclizing, β-seco-amyrin-forming)

Comments:

The enzyme from Arabidopsis thaliana is multifunctional and produces about equal amounts of α- and β-seco-amyrin. See EC 5.4.99.52, α-seco-amyrin synthase.

Links to other databases:

References:

1.	Shibuya, M., Xiang, T., Katsube, Y., Otsuka, M., Zhang, H. and Ebizuka, Y. Origin of structural diversity in natural triterpenes: direct synthesis of seco-triterpene skeletons by oxidosqualene cyclase. J. Am. Chem. Soc. 129 (2007) 1450–1455. [DOI] [PMID: 17263431]

[EC 5.4.99.54 created 2011]

5.4.99.55

Accepted name:

δ-amyrin synthase

Reaction:

(3S)-2,3-epoxy-2,3-dihydrosqualene = δ-amyrin

For diagram of α-amyrin, α-seco-amyrin and germanicol biosynthesis, click here

Other name(s):

SlTTS2 (gene name)

Systematic name:

(3S)-2,3-epoxy-2,3-dihydrosqualene mutase (cyclizing, δ-amyrin-forming)

Comments:

The enzyme from tomato (Solanum lycopersicum) gives 48% δ-amyrin, 18% α-amyrin, 13% β-amyrin and traces of three or four other triterpenoid alcohols [1]. See also EC 5.4.99.40, α-amyrin synthase and EC 5.4.99.39, β-amyrin synthase.

Links to other databases:

References:

1.	Wang, Z., Guhling, O., Yao, R., Li, F., Yeats, T.H., Rose, J.K. and Jetter, R. Two oxidosqualene cyclases responsible for biosynthesis of tomato fruit cuticular triterpenoids. Plant Physiol. 155 (2011) 540–552. [DOI] [PMID: 21059824]

[EC 5.4.99.55 created 2011]

5.4.99.56

Accepted name:

tirucalladienol synthase

Reaction:

(3S)-2,3-epoxy-2,3-dihydrosqualene = tirucalla-7,24-dien-3β-ol

For diagram of dammarenediol II and tirucalla-7,24-dien-3β-ol biosynthesis, click here

Other name(s):

PEN3

Systematic name:

(3S)-2,3-epoxy-2,3-dihydrosqualene mutase (cyclizing, tirucalla-7,24-dien-3β-ol-forming)

Comments:

The product from Arabidopsis thaliana is 85% tirucalla-7,24-dien-3β-ol with trace amounts of other triterpenoids.

Links to other databases:

References:

1.	Morlacchi, P., Wilson, W.K., Xiong, Q., Bhaduri, A., Sttivend, D., Kolesnikova, M.D. and Matsuda, S.P. Product profile of PEN3: the last unexamined oxidosqualene cyclase in Arabidopsis thaliana. Org. Lett. 11 (2009) 2627–2630. [DOI] [PMID: 19445469]

[EC 5.4.99.56 created 2011]

5.5.1.18

Accepted name:

lycopene ε-cyclase

Reaction:

carotenoid ψ-end group = carotenoid ε-end group

For diagram of α-, β-, γ-, δ- and ε-carotene biosynthesis, click here and for diagram of reaction, click here

Other name(s):

CrtL-e; LCYe; carotenoid ψ-end group lyase (decyclizing)

Systematic name:

carotenoid ψ-end group lyase (ring-opening)

Comments:

The carotenoid lycopene has the ψ-end group at both ends. When acting on one end, this enzyme forms δ-carotene. When acting on both ends, it forms ε-carotene.

Links to other databases:

References:

1.	Cunningham, F.X., Jr. and Gantt, E. One ring or two? Determination of ring number in carotenoids by lycopene ε-cyclases. Proc. Natl. Acad. Sci. USA 98 (2001) 2905–2910. [DOI] [PMID: 11226339]
2.	Stickforth, P., Steiger, S., Hess, W.R. and Sandmann, G. A novel type of lycopene ε-cyclase in the marine cyanobacterium Prochlorococcus marinus MED4. Arch. Microbiol. 179 (2003) 409–415. [DOI] [PMID: 12712234]

[EC 5.5.1.18 created 2011]

5.5.1.19

Accepted name:

lycopene β-cyclase

Reaction:

carotenoid ψ-end group = carotenoid β-end group

For diagram of α-, β-, γ-, δ- and ε-carotene biosynthesis, click here, for diagram of reaction, click here and for diagram of 5.5.1.19, click here

Other name(s):

CrtL; CrtL-b; CrtY; LCYb; carotenoid β-end group lyase (decyclizing)

Systematic name:

carotenoid β-end group lyase (ring-opening)

Comments:

The enzyme is a non-redox flavoprotein, containing FADH₂ that is used for stabilization of a transition state. Lycopene has a ψ-end group at both ends. When acting on one end, the enzyme forms γ-carotene. When acting on both ends it forms β-carotene. It also acts on neurosporene to give β-zeacarotene.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 220801-82-1

References:

1.	Cunningham, F.X., Jr., Chamovitz, D., Misawa, N., Gantt, E. and Hirschberg, J. Cloning and functional expression in Escherichia coli of a cyanobacterial gene for lycopene cyclase, the enzyme that catalyzes the biosynthesis of β-carotene. FEBS Lett. 328 (1993) 130–138. [DOI] [PMID: 8344419]
2.	Cunningham, F.X., Jr., Sun, Z., Chamovitz, D., Hirschberg, J. and Gantt, E. Molecular structure and enzymatic function of lycopene cyclase from the cyanobacterium Synechococcus sp strain PCC7942. Plant Cell 6 (1994) 1107–1121. [DOI] [PMID: 7919981]
3.	Hugueney, P., Badillo, A., Chen, H.C., Klein, A., Hirschberg, J., Camara, B. and Kuntz, M. Metabolism of cyclic carotenoids: a model for the alteration of this biosynthetic pathway in Capsicum annuum chromoplasts. Plant J. 8 (1995) 417–424. [DOI] [PMID: 7550379]
4.	Pecker, I., Gabbay, R., Cunningham, F.X., Jr. and Hirschberg, J. Cloning and characterization of the cDNA for lycopene β-cyclase from tomato reveals decrease in its expression during fruit ripening. Plant Mol. Biol. 30 (1996) 807–819. [PMID: 8624411]
5.	Hornero-Mendez, D. and Britton, G. Involvement of NADPH in the cyclization reaction of carotenoid biosynthesis. FEBS Lett. 515 (2002) 133–136. [DOI] [PMID: 11943208]
6.	Maresca, J.A., Graham, J.E., Wu, M., Eisen, J.A. and Bryant, D.A. Identification of a fourth family of lycopene cyclases in photosynthetic bacteria. Proc. Natl. Acad. Sci. USA 104 (2007) 11784–11789. [DOI] [PMID: 17606904]
7.	Yu, Q., Schaub, P., Ghisla, S., Al-Babili, S., Krieger-Liszkay, A. and Beyer, P. The lycopene cyclase CrtY from Pantoea ananatis (formerly Erwinia uredovora) catalyzes an FADred-dependent non-redox reaction. J. Biol. Chem. 285 (2010) 12109–12120. [DOI] [PMID: 20178989]

[EC 5.5.1.19 created 2011]

5.5.1.20

Accepted name:

prosolanapyrone-III cycloisomerase

Reaction:

prosolanapyrone III = (–)-solanapyrone A

For diagram of solanapyrone biosynthesis, click here

Glossary:

prosolanapyrone III = 4-methoxy-2-oxo-6-(1E,7E,9E)-undeca-1,7,9-trien-1-yl-2H-pyran-3-carboxaldehyde
(–)-solanapyrone A = 4-methoxy-6-((1R,2S,4aR,8aR)-2-methyl-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl)-2-oxo-2H-pyran-3-carboxaldehyde

Other name(s):

Sol5 (ambiguous); SPS (ambiguous); solanapyrone synthase (bifunctional enzyme: prosolanapyrone II oxidase/prosolanapyrone III cyclosiomerase)

Systematic name:

prosolanapyrone-III:(–)-solanapyrone A isomerase

Comments:

The enzyme is involved in the biosynthesis of the phytotoxin solanapyrone in some fungi. The bifunctional enzyme catalyses the oxidation of prosolanapyrone II and the subsequent Diels Alder cycloisomerization of the product prosolanapyrone III to (–)-solanapyrone A (cf. EC 1.1.3.42, prosolanapyrone II oxidase).

Links to other databases: