Proposed Changes to the Enzyme List

References:

1.	Mayer, J., Huhn, T., Habeck, M., Denger, K., Hollemeyer, K. and Cook, A.M. 2,3-Dihydroxypropane-1-sulfonate degraded by Cupriavidus pinatubonensis JMP134: purification of dihydroxypropanesulfonate 3-dehydrogenase. Microbiology 156 (2010) 1556–1564. [DOI] [PMID: 20150239]

[EC 1.1.1.308 created 2011]

1.1.1.309

Accepted name:

phosphonoacetaldehyde reductase (NADH)

Reaction:

2-hydroxyethylphosphonate + NAD⁺ = phosphonoacetaldehyde + NADH + H⁺

For diagram of phosphonate metabolism, click here

Other name(s):

PhpC

Systematic name:

2-hydroxyethylphosphonate:NAD⁺ oxidoreductase

Comments:

The enzyme from Streptomyces viridochromogenes catalyses a step in the biosynthesis of phosphinothricin tripeptide, the reduction of phosphonoacetaldehyde to 2-hydroxyethylphosphonate. The preferred cofactor is NADH, lower activity with NADPH [1].

Links to other databases:

References:

1.	Blodgett, J.A., Thomas, P.M., Li, G., Velasquez, J.E., van der Donk, W.A., Kelleher, N.L. and Metcalf, W.W. Unusual transformations in the biosynthesis of the antibiotic phosphinothricin tripeptide. Nat. Chem. Biol. 3 (2007) 480–485. [DOI] [PMID: 17632514]

[EC 1.1.1.309 created 2011]

1.1.1.310

Accepted name:

(S)-sulfolactate dehydrogenase

Reaction:

(2S)-3-sulfolactate + NAD⁺ = 3-sulfopyruvate + NADH + H⁺

Other name(s):

(2S)-3-sulfolactate dehydrogenase; SlcC

Systematic name:

(2S)-sulfolactate:NAD⁺ oxidoreductase

Comments:

This enzyme, isolated from the bacterium Chromohalobacter salexigens DSM 3043, acts only on the (S)-enantiomer of 3-sulfolactate. Combined with EC 1.1.1.338, (2R)-3-sulfolactate dehydrogenase (NADP⁺), it provides a racemase system that converts (2S)-3-sulfolactate to (2R)-3-sulfolactate, which is degraded further by EC 4.4.1.24, (2R)-sulfolactate sulfo-lyase. The enzyme is specific for NAD⁺.

Links to other databases:

References:

1.	Denger, K. and Cook, A.M. Racemase activity effected by two dehydrogenases in sulfolactate degradation by Chromohalobacter salexigens: purification of (S)-sulfolactate dehydrogenase. Microbiology 156 (2010) 967–974. [DOI] [PMID: 20007648]

[EC 1.1.1.310 created 2011, modified 2013]

1.1.1.311

Accepted name:

(S)-1-phenylethanol dehydrogenase

Reaction:

(S)-1-phenylethanol + NAD⁺ = acetophenone + NADH + H⁺

Other name(s):

PED

Systematic name:

(S)-1-phenylethanol:NAD⁺ oxidoreductase

Comments:

The enzyme is involved in degradation of ethylbenzene.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, KEGG, PDB

References:

1.	Kniemeyer, O. and Heider, J. (S)-1-phenylethanol dehydrogenase of Azoarcus sp. strain EbN1, an enzyme of anaerobic ethylbenzene catabolism. Arch. Microbiol. 176 (2001) 129–135. [PMID: 11479712]
2.	Hoffken, H.W., Duong, M., Friedrich, T., Breuer, M., Hauer, B., Reinhardt, R., Rabus, R. and Heider, J. Crystal structure and enzyme kinetics of the (S)-specific 1-phenylethanol dehydrogenase of the denitrifying bacterium strain EbN1. Biochemistry 45 (2006) 82–93. [DOI] [PMID: 16388583]

[EC 1.1.1.311 created 2011]

1.1.5.8

Accepted name:

quinate/shikimate dehydrogenase (quinone)

Reaction:

quinate + quinone = 3-dehydroquinate + quinol

For diagram of shikimate and chorismate biosynthesis, click here

Glossary:

quinate = (1R,3R,4R,5R)-1,3,4,5-tetrahydroxycyclohexanecarboxylic acid and is a cyclitol carboxylate
The numbering system used for the 3-dehydroquinate is that of the recommendations on cyclitols, sections I-8 and I-9: and is shown in the reaction diagram. The use of the term '5-dehydroquinate' for this compound is based on an earlier system of numbering.

Other name(s):

NAD(P)⁺-independent quinate dehydrogenase; quinate:pyrroloquinoline-quinone 5-oxidoreductase; quinate dehydrogenase (quinone)

Systematic name:

quinate:quinol 3-oxidoreductase

Comments:

The enzyme is membrane-bound. Does not use NAD(P)⁺ as acceptor. Contains pyrroloquinoline-quinone. cf. EC 1.1.1.24, quinate/shikimate dehydrogenase (NAD⁺), EC 1.1.1.282, quinate/shikimate dehydrogenase [NAD(P)⁺], and EC 1.1.1.25, shikimate dehydrogenase (NADP⁺).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 115299-99-5

References:

1.	van Kleef, M.A.G. and Duine, J.A. Bacterial NAD(P)-independent quinate dehydrogenase is a quinoprotein. Arch. Microbiol. 150 (1988) 32–36. [PMID: 3044290]
2.	Adachi, O., Tanasupawat, S., Yoshihara, N., Toyama, H. and Matsushita, K. 3-Dehydroquinate production by oxidative fermentation and further conversion of 3-dehydroquinate to the intermediates in the shikimate pathway. Biosci. Biotechnol. Biochem. 67 (2003) 2124–2131. [DOI] [PMID: 14586099]
3.	Vangnai, A.S., Toyama, H., De-Eknamkul, W., Yoshihara, N., Adachi, O. and Matsushita, K. Quinate oxidation in Gluconobacter oxydans IFO3244: purification and characterization of quinoprotein quinate dehydrogenase. FEMS Microbiol. Lett. 241 (2004) 157–162. [DOI] [PMID: 15598527]

[EC 1.1.5.8 created 1992 as EC 1.1.99.25, modified 2004, transferred 2010 to EC 1.1.5.8, modified 2021]

1.1.98.2

Accepted name:

glucose-6-phosphate dehydrogenase (coenzyme-F₄₂₀)

Reaction:

D-glucose 6-phosphate + oxidized coenzyme F₄₂₀ = 6-phospho-D-glucono-1,5-lactone + reduced coenzyme F₄₂₀

Other name(s):

coenzyme F₄₂₀-dependent glucose-6-phosphate dehydrogenase; F₄₂₀-dependent glucose-6-phosphate dehydrogenase; FGD1; Rv0407; F₄₂₀-dependent glucose-6-phosphate dehydrogenase 1

Systematic name:

D-glucose-6-phosphate:F420 1-oxidoreductase

Comments:

The enzyme is very specific for D-glucose 6-phosphate. No activity with NAD⁺, NADP⁺, FAD and FMN [1].

Links to other databases:

References:

1.	Purwantini, E. and Daniels, L. Purification of a novel coenzyme F₄₂₀-dependent glucose-6-phosphate dehydrogenase from Mycobacterium smegmatis. J. Bacteriol. 178 (1996) 2861–2866. [DOI] [PMID: 8631674]
2.	Bashiri, G., Squire, C.J., Baker, E.N. and Moreland, N.J. Expression, purification and crystallization of native and selenomethionine labeled Mycobacterium tuberculosis FGD1 (Rv0407) using a Mycobacterium smegmatis expression system. Protein Expr. Purif. 54 (2007) 38–44. [DOI] [PMID: 17376702]
3.	Purwantini, E., Gillis, T.P. and Daniels, L. Presence of F₄₂₀-dependent glucose-6-phosphate dehydrogenase in Mycobacterium and Nocardia species, but absence from Streptomyces and Corynebacterium species and methanogenic Archaea. FEMS Microbiol. Lett. 146 (1997) 129–134. [DOI] [PMID: 8997717]

[EC 1.1.98.2 created 2010 as EC 1.1.99.34, transferred 2011 to EC 1.1.98.2]

1.1.99.25

Transferred entry:

quinate dehydrogenase (pyrroloquinoline-quinone). Now EC 1.1.5.8, quinate dehydrogenase (quinone)

[EC 1.1.99.25 created 1992, modified 2004, deleted 2010]

1.1.99.34

Transferred entry:

glucose-6-phosphate dehydrogenase (coenzyme-F₄₂₀). As the acceptor is now known, the enzyme has been transferred to EC 1.1.98.2, glucose-6-phosphate dehydrogenase (coenzyme-F₄₂₀)

[EC 1.1.99.34 created 2010, deleted 2011]

*EC

1.2.1.8

Accepted name:

betaine-aldehyde dehydrogenase

Reaction:

betaine aldehyde + NAD⁺ + H₂O = betaine + NADH + 2 H⁺

Glossary:

betaine = glycine betaine = N,N,N-trimethylglycine = N,N,N-trimethylammonioacetate
betaine aldehyde = N,N,N-trimethyl-2-oxoethylammonium

Other name(s):

betaine aldehyde oxidase; BADH; betaine aldehyde dehydrogenase; BetB

Systematic name:

betaine-aldehyde:NAD⁺ oxidoreductase

Comments:

In many bacteria, plants and animals, the osmoprotectant betaine is synthesized in two steps: (1) choline to betaine aldehyde and (2) betaine aldehyde to betaine. This enzyme is involved in the second step and appears to be the same in plants, animals and bacteria. In contrast, different enzymes are involved in the first reaction. In plants, this reaction is catalysed by EC 1.14.15.7 (choline monooxygenase), whereas in animals and many bacteria it is catalysed by either membrane-bound EC 1.1.99.1 (choline dehydrogenase) or soluble EC 1.1.3.17 (choline oxidase) [5]. In some bacteria, betaine is synthesized from glycine through the actions of EC 2.1.1.156 (glycine/sarcosine N-methyltransferase) and EC 2.1.1.157 (sarcosine/dimethylglycine N-methyltransferase).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9028-90-4

References:

1.	Rothschild, H.A. and Barron, E.S.G. The oxidation of betaine aldehyde by betaine aldehyde dehydrogenase. J. Biol. Chem. 209 (1954) 511–523. [PMID: 13192104]
2.	Livingstone, J.R., Maruo, T., Yoshida, I., Tarui, Y., Hirooka, K., Yamamoto, Y., Tsutui, N. and Hirasawa, E. Purification and properties of betaine aldehyde dehydrogenase from Avena sativa. J. Plant Res. 116 (2003) 133–140. [DOI] [PMID: 12736784]
3.	Muñoz-Clares, R.A., González-Segura, L., Mújica-Jiménez, C. and Contreras-Diaz, L. Ligand-induced conformational changes of betaine aldehyde dehydrogenase from Pseudomonas aeruginosa and Amaranthus hypochondriacus L. leaves affecting the reactivity of the catalytic thiol. Chem. Biol. Interact. (2003) 129–137. [DOI] [PMID: 12604197]
4.	Johansson, K., El-Ahmad, M., Ramaswamy, S., Hjelmqvist, L., Jornvall, H. and Eklund, H. Structure of betaine aldehyde dehydrogenase at 2.1 Å resolution. Protein Sci. 7 (1998) 2106–2117. [DOI] [PMID: 9792097]
5.	Waditee, R., Tanaka, Y., Aoki, K., Hibino, T., Jikuya, H., Takano, J., Takabe, T. and Takabe, T. Isolation and functional characterization of N-methyltransferases that catalyze betaine synthesis from glycine in a halotolerant photosynthetic organism Aphanothece halophytica. J. Biol. Chem. 278 (2003) 4932–4942. [DOI] [PMID: 12466265]

[EC 1.2.1.8 created 1961, modified 2005, modified 2011]

*EC

1.2.1.10

Accepted name:

acetaldehyde dehydrogenase (acetylating)

Reaction:

acetaldehyde + CoA + NAD⁺ = acetyl-CoA + NADH + H⁺

For diagram of 3-phenylpropanoate catabolism, click here, for diagram of catechol catabolism (meta ring cleavage), click here and for diagram of cinnamate catabolism, click here

Other name(s):

aldehyde dehydrogenase (acylating); ADA; acylating acetaldehyde dehyrogenase; DmpF; BphJ

Systematic name:

acetaldehyde:NAD⁺ oxidoreductase (CoA-acetylating)

Comments:

Also acts, more slowly, on glycolaldehyde, propanal and butanal. In several bacterial species this enzyme forms a bifunctional complex with EC 4.1.3.39, 4-hydroxy-2-oxovalerate aldolase. The enzymes from the bacteria Burkholderia xenovorans and Thermus thermophilus also perform the reaction of EC 1.2.1.87, propanal dehydrogenase (propanoylating). Involved in the meta-cleavage pathway for the degradation of phenols, methylphenols and catechols. NADP⁺ can replace NAD⁺ but the rate of reaction is much slower [3].

Links to other databases:

BRENDA, EXPASY, Gene, GTD, KEGG, PDB, CAS registry number: 9028-91-5

References:

1.	Burton, R.M. and Stadtman, E.R. The oxidation of acetaldehyde to acetyl coenzyme A. J. Biol. Chem. 202 (1953) 873–890. [PMID: 13061511]
2.	Smith, L.T. and Kaplan, N.O. Purification, properties, and kinetic mechanism of coenzyme A-linked aldehyde dehydrogenase from Clostridium kluyveri. Arch. Biochem. Biophys. 203 (1980) 663–675. [DOI] [PMID: 7458347]
3.	Powlowski, J., Sahlman, L. and Shingler, V. Purification and properties of the physically associated meta-cleavage pathway enzymes 4-hydroxy-2-ketovalerate aldolase and aldehyde dehydrogenase (acylating) from Pseudomonas sp. strain CF600. J. Bacteriol. 175 (1993) 377–385. [DOI] [PMID: 8419288]
4.	Baker, P., Pan, D., Carere, J., Rossi, A., Wang, W. and Seah, S.Y.K. Characterization of an aldolase-dehydrogenase complex that exhibits substrate channeling in the polychlorinated biphenyls degradation pathway. Biochemistry 48 (2009) 6551–6558. [DOI] [PMID: 19476337]
5.	Baker, P., Hillis, C., Carere, J. and Seah, S.Y.K. Protein-protein interactions and substrate channeling in orthologous and chimeric aldolase-dehydrogenase complexes. Biochemistry 51 (2012) 1942–1952. [DOI] [PMID: 22316175]

[EC 1.2.1.10 created 1961, modified 2006, modified 2011]

*EC

1.2.1.65

Accepted name:

salicylaldehyde dehydrogenase

Reaction:

salicylaldehyde + NAD⁺ + H₂O = salicylate + NADH + 2 H⁺

For diagram of naphthalene metabolism, click here

Glossary:

salicylaldehyde = 2-hydroxybenzaldehyde

Systematic name:

salicylaldehyde:NAD⁺ oxidoreductase

Comments:

Involved in the naphthalene degradation pathway in some bacteria.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 55354-34-2

References:

1.	Eaton, R. and Chapman, P.J. Bacterial metabolism of naphthalene: construction and use of recombinant bacteria to study ring cleavage of 1,2-dihydroxynaphthalene and subsequent reactions. J. Bacteriol. 174 (1992) 7542–7554. [DOI] [PMID: 1447127]

[EC 1.2.1.65 created 2000, modified 2011]

1.2.1.80

Accepted name:

long-chain acyl-[acyl-carrier-protein] reductase

Reaction:

a long-chain aldehyde + an [acyl-carrier protein] + NAD(P)⁺ = a long-chain acyl-[acyl-carrier protein] + NAD(P)H + H⁺

Glossary:

a long-chain aldehyde = an aldehyde derived from a fatty acid with an aliphatic chain of 13-22 carbons.
an [acyl-carrier protein] = ACP = [acp]

Other name(s):

long-chain acyl-[acp] reductase; fatty acyl-[acyl-carrier-protein] reductase; acyl-[acp] reductase

Systematic name:

long-chain-aldehyde:NAD(P)⁺ oxidoreductase (acyl-[acyl-carrier protein]-forming)

Comments:

Catalyses the reaction in the opposite direction. This enzyme, purified from the cyanobacterium Synechococcus elongatus PCC 7942, catalyses the NAD(P)H-dependent reduction of an activated fatty acid (acyl-[acp]) to the corresponding aldehyde. Together with EC 4.1.99.5, octadecanal decarbonylase, it is involved in alkane biosynthesis. The natural substrates of the enzyme are C₁₆ and C₁₈ activated fatty acids. Requires Mg²⁺.

Links to other databases:

References:

1.	Schirmer, A., Rude, M.A., Li, X., Popova, E. and del Cardayre, S.B. Microbial biosynthesis of alkanes. Science 329 (2010) 559–562. [DOI] [PMID: 20671186]

[EC 1.2.1.80 created 2011]

1.2.2.2

Deleted entry:

pyruvate dehydrogenase (cytochrome). Now covered by EC 1.2.5.1, pyruvate dehydrogenase (quinone)

[EC 1.2.2.2 created 1961, deleted 2010]

1.3.1.85

Accepted name:

crotonyl-CoA carboxylase/reductase

Reaction:

(2S)-ethylmalonyl-CoA + NADP⁺ = (E)-but-2-enoyl-CoA + CO₂ + NADPH + H⁺

Glossary:

(E)-but-2-enoyl-CoA = crotonyl-CoA

Other name(s):

CCR; crotonyl-CoA reductase (carboxylating)

Systematic name:

(2S)-ethylmalonyl-CoA:NADP⁺ oxidoreductase (decarboxylating)

Comments:

The reaction is catalysed in the reverse direction. This enzyme, isolated from the bacterium Rhodobacter sphaeroides, catalyses (E)-but-2-enoyl-CoA-dependent oxidation of NADPH in the presence of CO₂. When CO₂ is absent, the enzyme catalyses the reduction of (E)-but-2-enoyl-CoA to butanoyl-CoA, but with only 10% of maximal activity (relative to (E)-but-2-enoyl-CoA carboxylation).

Links to other databases:

References:

1.	Erb, T.J., Berg, I.A., Brecht, V., Muller, M., Fuchs, G. and Alber, B.E. Synthesis of C₅-dicarboxylic acids from C₂-units involving crotonyl-CoA carboxylase/reductase: the ethylmalonyl-CoA pathway. Proc. Natl. Acad. Sci. USA 104 (2007) 10631–10636. [DOI] [PMID: 17548827]
2.	Erb, T.J., Brecht, V., Fuchs, G., Muller, M. and Alber, B.E. Carboxylation mechanism and stereochemistry of crotonyl-CoA carboxylase/reductase, a carboxylating enoyl-thioester reductase. Proc. Natl. Acad. Sci. USA 106 (2009) 8871–8876. [DOI] [PMID: 19458256]

[EC 1.3.1.85 created 2011]

1.3.1.86

Accepted name:

crotonyl-CoA reductase

Reaction:

butanoyl-CoA + NADP⁺ = (E)-but-2-enoyl-CoA + NADPH + H⁺

For diagram of lysine catabolism, click here

Glossary:

(E)-but-2-enoyl-CoA = crotonyl-CoA
butanoyl-CoA = butyryl-CoA

Other name(s):

butyryl-CoA dehydrogenase; butyryl dehydrogenase; unsaturated acyl-CoA reductase; ethylene reductase; enoyl-coenzyme A reductase; unsaturated acyl coenzyme A reductase; butyryl coenzyme A dehydrogenase; short-chain acyl CoA dehydrogenase; short-chain acyl-coenzyme A dehydrogenase; 3-hydroxyacyl CoA reductase; butanoyl-CoA:(acceptor) 2,3-oxidoreductase; CCR

Systematic name:

butanoyl-CoA:NADP⁺ 2,3-oxidoreductase

Comments:

Catalyses the reaction in the reverse direction. This enzyme from Streptomyces collinus is specific for (E)-but-2-enoyl-CoA, and is proposed to provide butanoyl-CoA as a starter unit for straight-chain fatty acid biosynthesis.

Links to other databases:

References:

Wallace, K.K., Bao, Z.Y., Dai, H., Digate, R., Schuler, G., Speedie, M.K. and Reynolds, K.A. Purification of crotonyl-CoA reductase from Streptomyces collinus and cloning, sequencing and expression of the corresponding gene in Escherichia coli. Eur. J. Biochem. 233 (1995) 954–962. [DOI] [PMID: 8521864]

[EC 1.3.1.86 created 2011]

1.3.5.4

Transferred entry:

fumarate reductase (quinol), now included in EC 1.3.5.1, succinate dehydrogenase.

[EC 1.3.5.4 created 2010, modified 2013, deleted 2022]

1.3.7.7

Accepted name:

ferredoxin:protochlorophyllide reductase (ATP-dependent)

Reaction:

chlorophyllide a + oxidized ferredoxin + 2 ADP + 2 phosphate = protochlorophyllide a + reduced ferredoxin + 2 ATP + 2 H₂O

For diagram of chlorophyll biosynthesis (later stages), click here

Other name(s):

light-independent protochlorophyllide reductase

Systematic name:

ATP-dependent ferredoxin:protochlorophyllide-a 7,8-oxidoreductase

Comments:

Occurs in photosynthetic bacteria, cyanobacteria, green algae and gymnosperms. The enzyme catalyses trans-reduction of the D-ring of protochlorophyllide; the product has the (7S,8S)-configuration. Unlike EC 1.3.1.33 (protochlorophyllide reductase), light is not required. The enzyme contains a [4Fe-4S] cluster, and structurally resembles the Fe protein/MoFe protein complex of nitrogenase (EC 1.18.6.1), which catalyses an ATP-driven reduction.

Links to other databases:

References:

1.	Fujita, Y., Matsumoto, H., Takahashi, Y. and Matsubara, H. Identification of a nifDK-like gene (ORF467) involved in the biosynthesis of chlorophyll in the cyanobacterium Plectonema boryanum. Plant Cell Physiol. 34 (1993) 305–314. [PMID: 8199775]
2.	Nomata, J., Ogawa, T., Kitashima, M., Inoue, K. and Fujita, Y. NB-protein (BchN-BchB) of dark-operative protochlorophyllide reductase is the catalytic component containing oxygen-tolerant Fe-S clusters. FEBS Lett. 582 (2008) 1346–1350. [DOI] [PMID: 18358835]
3.	Muraki, N., Nomata, J., Ebata, K., Mizoguchi, T., Shiba, T., Tamiaki, H., Kurisu, G. and Fujita, Y. X-ray crystal structure of the light-independent protochlorophyllide reductase. Nature 465 (2010) 110–114. [DOI] [PMID: 20400946]

[EC 1.3.7.7 created 2011, modified 2013]

1.5.3.18

Accepted name:

L-saccharopine oxidase

Reaction:

N⁶-(L-1,3-dicarboxypropyl)-L-lysine + H₂O + O₂ = (S)-2-amino-6-oxohexanoate + L-glutamate + H₂O₂

Glossary:

L-saccharopine = N⁶-(L-1,3-dicarboxypropyl)-L-lysine
(S)-2-amino-6-oxohexanoate = L-2-aminoadipate 6-semialdehyde = L-allysine

Other name(s):

FAP2

Systematic name:

L-saccharopine:oxygen oxidoreductase (L-glutamate-forming)

Comments:

The enzyme is involved in pipecolic acid biosynthesis. A flavoprotein (FAD).

Links to other databases:

References:

1.	Yoshida, N., Akazawa, S., Katsuragi, T. and Tani, Y. Characterization of two fructosyl-amino acid oxidase homologs of Schizosaccharomyces pombe. J. Biosci. Bioeng. 97 (2004) 278–280. [DOI] [PMID: 16233628]
2.	Wickwire, B.M., Wagner, C. and Broquist, H.P. Pipecolic acid biosynthesis in Rhizoctonia leguminicola. II. Saccharopine oxidase: a unique flavin enzyme involved in pipecolic acid biosynthesis. J. Biol. Chem. 265 (1990) 14748–14753. [PMID: 2394693]

[EC 1.5.3.18 created 2011]

1.6.5.8

Transferred entry:

NADH:ubiquinone reductase (Na⁺-transporting). Now EC 7.2.1.1, NADH:ubiquinone reductase (Na⁺-transporting)

[EC 1.6.5.8 created 2011, deleted 2018]

*EC

1.11.1.7

Accepted name:

peroxidase

Reaction:

2 phenolic donor + H₂O₂ = 2 phenoxyl radical of the donor + 2 H₂O

Other name(s):

lactoperoxidase; guaiacol peroxidase; plant peroxidase; Japanese radish peroxidase; horseradish peroxidase (HRP); soybean peroxidase (SBP); extensin peroxidase; heme peroxidase; oxyperoxidase; protoheme peroxidase; pyrocatechol peroxidase; scopoletin peroxidase; Coprinus cinereus peroxidase; Arthromyces ramosus peroxidase

Systematic name:

phenolic donor:hydrogen-peroxide oxidoreductase

Comments:

Heme proteins with histidine as proximal ligand. The iron in the resting enzyme is Fe(III). They also peroxidize non-phenolic substrates such as 3,3′,5,5′-tetramethylbenzidine (TMB) and 2,2′-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS). Certain peroxidases (e.g. lactoperoxidase, SBP) oxidize bromide, iodide and thiocyanate.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9003-99-0

References:

1.	Kenten, R.H. and Mann, P.J.G. Simple method for the preparation of horseradish peroxidase. Biochem. J. 57 (1954) 347–348. [PMID: 13172193]
2.	Morrison, M., Hamilton, H.B. and Stotz, E. The isolation and purification of lactoperoxidase by ion exchange chromatography. J. Biol. Chem. 228 (1957) 767–776. [PMID: 13475358]
3.	Paul, K.G. Peroxidases. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Ed.), The Enzymes, 2nd edn, vol. 8, Academic Press, New York, 1963, pp. 227–274.
4.	Tagawa, K., Shin, M. and Okunuki, K. Peroxidases from wheat germ. Nature (Lond.) 183 (1959) 111. [PMID: 13622706]
5.	Theorell, H. The preparation and some properties of crystalline horse-radish peroxidase. Ark. Kemi Mineral. Geol. 16A No. 2 (1943) 1–11.
6.	Farhangrazi, Z.S., Copeland, B.R., Nakayama, T., Amachi, T., Yamazaki, I. and Powers, L.S. Oxidation-reduction properties of compounds I and II of Arthromyces ramosus peroxidase. Biochemistry 33 (1994) 5647–5652. [PMID: 8180190]
7.	Aitken, M.D. and Heck, P.E. Turnover capacity of coprinus cinereus peroxidase for phenol and monosubstituted phenol. Biotechnol. Prog. 14 (1998) 487–492. [DOI] [PMID: 9622531]
8.	Dunford, H.B. Heme peroxidases, Wiley-VCH, New York, 1999, pp. 33–218.
9.	Torres, E and Ayala, M. Biocatalysis based on heme peroxidases, Springer, Berlin, 2010, pp. 7–110.

[EC 1.11.1.7 created 1961, modified 2011]

*EC

1.11.1.10

Accepted name:

chloride peroxidase

Reaction:

RH + chloride + H₂O₂ = RCl + 2 H₂O

Other name(s):

chloroperoxidase; CPO; vanadium haloperoxidase

Systematic name:

chloride:hydrogen-peroxide oxidoreductase

Comments:

Brings about the chlorination of a range of organic molecules, forming stable C-Cl bonds. Also oxidizes bromide and iodide. Enzymes of this type are either heme-thiolate proteins, or contain vanadate. A secreted enzyme produced by the ascomycetous fungus Caldariomyces fumago (Leptoxyphium fumago) is an example of the heme-thiolate type. It catalyses the production of hypochlorous acid by transferring one oxygen atom from H₂O₂ to chloride. At a separate site it catalyses the chlorination of activated aliphatic and aromatic substrates, via HClO and derived chlorine species. In the absence of halides, it shows peroxidase (e.g. phenol oxidation) and peroxygenase activities. The latter inserts oxygen from H₂O₂ into, for example, styrene (side chain epoxidation) and toluene (benzylic hydroxylation), however, these activities are less pronounced than its activity with halides. Has little activity with non-activated substrates such as aromatic rings, ethers or saturated alkanes. The chlorinating peroxidase produced by ascomycetous fungi (e.g. Curvularia inaequalis) is an example of a vanadium chloroperoxidase, and is related to bromide peroxidase (EC 1.11.1.18). It contains vanadate and oxidizes chloride, bromide and iodide into hypohalous acids. In the absence of halides, it peroxygenates organic sulfides and oxidizes ABTS [2,2′-azinobis(3-ethylbenzthiazoline-6-sulfonic acid)] but no phenols.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9055-20-3

References:

1.	Morris, D.R. and Hager, L.P. Chloroperoxidase. I. Isolation and properties of the crystalline glycoprotein. J. Biol. Chem. 241 (1966) 1763–1768. [PMID: 5949836]
2.	Hager, L.P., Hollenberg, P.F., Rand-Meir, T., Chiang, R. and Doubek, D.L. Chemistry of peroxidase intermediates. Ann. N.Y. Acad. Sci. 244 (1975) 80–93. [DOI] [PMID: 1056179]
3.	Theiler, R., Cook, J.C., Hager, L.P. and Siuda, J.F. Halohydrocarbon synthesis by bromoperoxidase. Science 202 (1978) 1094–1096. [DOI] [PMID: 17777960]
4.	Sundaramoorthy, M., Terner, J. and Poulos, T.L. The crystal structure of chloroperoxidase: a heme peroxidase^--cytochrome P450 functional hybrid. Structure 3 (1995) 1367–1377. [DOI] [PMID: 8747463]
5.	ten Brink, H.B., Tuynman, A., Dekker, H.L., Hemrika, W., Izumi, Y., Oshiro, T., Schoemaker, H.E. and Wever, R. Enantioselective sulfoxidation catalyzed by vanadium haloperoxidases. Inorg. Chem. 37 (1998) 6780–6784. [DOI] [PMID: 11670813]
6.	ten Brink, H.B., Dekker, H.L., Schoemaker, H.E. and Wever, R. Oxidation reactions catalyzed by vanadium chloroperoxidase from Curvularia inaequalis. J. Inorg. Biochem. 80 (2000) 91–98. [DOI] [PMID: 10885468]
7.	Manoj, K.M. Chlorinations catalyzed by chloroperoxidase occur via diffusible intermediate(s) and the reaction components play multiple roles in the overall process. Biochim. Biophys. Acta 1764 (2006) 1325–1339. [DOI] [PMID: 16870515]
8.	Kuhnel, K., Blankenfeldt, W., Terner, J. and Schlichting, I. Crystal structures of chloroperoxidase with its bound substrates and complexed with formate, acetate, and nitrate. J. Biol. Chem. 281 (2006) 23990–23998. [DOI] [PMID: 16790441]
9.	Manoj, K.M. and Hager, L.P. Chloroperoxidase, a janus enzyme. Biochemistry 47 (2008) 2997–3003. [DOI] [PMID: 18220360]

[EC 1.11.1.10 created 1972, modified 2011]

1.11.1.19

Accepted name:

dye decolorizing peroxidase

Reaction:

Reactive Blue 5 + 2 H₂O₂ = phthalate + 2,2′-disulfonyl azobenzene + 3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]benzenesulfonate + 2 H₂O

Glossary:

Reactive Blue 5 = 1-amino-4-{[3-({4-chloro-6-[(3-sulfophenyl)amino]-1,3,5-triazin-2-yl}amino)-4-sulfophenyl]amino}-9,10-dihydro-9,10-dioxoanthracene-2-sulfonic acid

Other name(s):

DyP; DyP-type peroxidase

Systematic name:

Reactive-Blue-5:hydrogen-peroxide oxidoreductase

Comments:

Heme proteins with proximal histidine secreted by basidiomycetous fungi and eubacteria. They are similar to EC 1.11.1.16 versatile peroxidase (oxidation of Reactive Black 5, phenols, veratryl alcohol), but differ from the latter in their ability to efficiently oxidize a number of recalcitrant anthraquinone dyes, and inability to oxidize Mn(II). The model substrate Reactive Blue 5 is converted with high efficiency via a so far unique mechanism that combines oxidative and hydrolytic steps and leads to the formation of phthalic acid. Bacterial TfuDyP catalyses sulfoxidation.

Links to other databases:

References:

1.	Kim, S.J. and Shoda, M. Purification and characterization of a novel peroxidase from Geotrichum candidum dec 1 involved in decolorization of dyes. Appl. Environ. Microbiol. 65 (1999) 1029–1035. [PMID: 10049859]
2.	Sugano, Y., Ishii, Y. and Shoda, M. Role of H164 in a unique dye-decolorizing heme peroxidase DyP. Biochem. Biophys. Res. Commun. 322 (2004) 126–132. [DOI] [PMID: 15313183]
3.	Zubieta, C., Joseph, R., Krishna, S.S., McMullan, D., Kapoor, M., Axelrod, H.L., Miller, M.D., Abdubek, P., Acosta, C., Astakhova, T., Carlton, D., Chiu, H.J., Clayton, T., Deller, M.C., Duan, L., Elias, Y., Elsliger, M.A., Feuerhelm, J., Grzechnik, S.K., Hale, J., Han, G.W., Jaroszewski, L., Jin, K.K., Klock, H.E., Knuth, M.W., Kozbial, P., Kumar, A., Marciano, D., Morse, A.T., Murphy, K.D., Nigoghossian, E., Okach, L., Oommachen, S., Reyes, R., Rife, C.L., Schimmel, P., Trout, C.V., van den Bedem, H., Weekes, D., White, A., Xu, Q., Hodgson, K.O., Wooley, J., Deacon, A.M., Godzik, A., Lesley, S.A. and Wilson, I.A. Identification and structural characterization of heme binding in a novel dye-decolorizing peroxidase, TyrA. Proteins 69 (2007) 234–243. [DOI] [PMID: 17654547]
4.	Sugano, Y., Matsushima, Y., Tsuchiya, K., Aoki, H., Hirai, M. and Shoda, M. Degradation pathway of an anthraquinone dye catalyzed by a unique peroxidase DyP from Thanatephorus cucumeris Dec 1. Biodegradation 20 (2009) 433–440. [DOI] [PMID: 19009358]
5.	Sugano, Y. DyP-type peroxidases comprise a novel heme peroxidase family. Cell. Mol. Life Sci. 66 (2009) 1387–1403. [DOI] [PMID: 19099183]
6.	Ogola, H.J., Kamiike, T., Hashimoto, N., Ashida, H., Ishikawa, T., Shibata, H. and Sawa, Y. Molecular characterization of a novel peroxidase from the cyanobacterium Anabaena sp. strain PCC 7120. Appl. Environ. Microbiol. 75 (2009) 7509–7518. [DOI] [PMID: 19801472]
7.	van Bloois, E., Torres Pazmino, D.E., Winter, R.T. and Fraaije, M.W. A robust and extracellular heme-containing peroxidase from Thermobifida fusca as prototype of a bacterial peroxidase superfamily. Appl. Microbiol. Biotechnol. 86 (2010) 1419–1430. [DOI] [PMID: 19967355]
8.	Liers, C., Bobeth, C., Pecyna, M., Ullrich, R. and Hofrichter, M. DyP-like peroxidases of the jelly fungus Auricularia auricula-judae oxidize nonphenolic lignin model compounds and high-redox potential dyes. Appl. Microbiol. Biotechnol. 85 (2010) 1869–1879. [DOI] [PMID: 19756587]
9.	Hofrichter, M., Ullrich, R., Pecyna, M.J., Liers, C. and Lundell, T. New and classic families of secreted fungal heme peroxidases. Appl. Microbiol. Biotechnol. 87 (2010) 871–897. [DOI] [PMID: 20495915]

[EC 1.11.1.19 created 2011, modified 2015]

1.11.1.20

Accepted name:

prostamide/prostaglandin F_2α synthase

Reaction:

thioredoxin + (5Z,9α,11α,13E,15S)-9,11-epidioxy-15-hydroxy-prosta-5,13-dienoate = thioredoxin disulfide + (5Z,9α,11α,13E,15S)-9,11,15-trihydroxyprosta-5,13-dienoate

Glossary:

prostamide H₂ = (5Z)-N-(2-hydroxyethyl)-7-{(1R,4S,5R,6R)-6-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-2,3-dioxabicyclo[2.2.1]hept-5-yl}hept-5-enamide
prostamide F_2α = (5Z,9α,11α,13E,15S)-9,11,15-trihydroxy-N-(2-hydroxyethyl)prosta-5,13-dien-1-amide
prostaglandin H₂ = (5Z,9α,11α,13E,15S)-9,11-epidioxy-15-hydroxy-prosta-5,13-dienoate
prostaglandin F_2α = (5Z,9α,11α,13E,15S)-9,11,15-trihydroxyprosta-5,13-dienoate

Other name(s):

prostamide/PGF synthase; prostamide F synthase; prostamide/prostaglandin F synthase; tPGF synthase

Systematic name:

thioredoxin:(5Z,9α,11α,13E,15S)-9,11-epidioxy-15-hydroxy-prosta-5,13-dienoate oxidoreductase

Comments:

The enzyme contains a thioredoxin-type disulfide as a catalytic group. Prostamide H₂ and prostaglandin H₂ are the best substrates; the latter is converted to prostaglandin F_2α. The enzyme also reduces tert-butyl hydroperoxide, cumene hydroperoxide and H₂O₂, but not prostaglandin D₂ or prostaglandin E₂.

Links to other databases:

References:

1.	Moriuchi, H., Koda, N., Okuda-Ashitaka, E., Daiyasu, H., Ogasawara, K., Toh, H., Ito, S., Woodward, D.F. and Watanabe, K. Molecular characterization of a novel type of prostamide/prostaglandin F synthase, belonging to the thioredoxin-like superfamily. J. Biol. Chem. 283 (2008) 792–801. [DOI] [PMID: 18006499]
2.	Yoshikawa, K., Takei, S., Hasegawa-Ishii, S., Chiba, Y., Furukawa, A., Kawamura, N., Hosokawa, M., Woodward, D.F., Watanabe, K. and Shimada, A. Preferential localization of prostamide/prostaglandin F synthase in myelin sheaths of the central nervous system. Brain Res. 1367 (2011) 22–32. [DOI] [PMID: 20950588]

[EC 1.11.1.20 created 2011]

1.11 Acting on a peroxide as acceptor

1.11.2 Peroxygenases

1.11.2.1

Accepted name:

unspecific peroxygenase

Reaction:

RH + H₂O₂ = ROH + H₂O

Other name(s):

aromatic peroxygenase; mushroom peroxygenase; haloperoxidase-peroxygenase; Agrocybe aegerita peroxidase

Systematic name:

substrate:hydrogen-peroxide oxidoreductase (RH-hydroxylating or -epoxidising)

Comments:

A heme-thiolate protein (P-450). Enzymes of this type include glycoproteins secreted by agaric basidiomycetes. They catalyse the insertion of an oxygen atom from H₂O₂ into a wide variety of substrates, including aromatic rings such as naphthalene, toluene, phenanthrene, pyrene and p-nitrophenol, recalcitrant heterocycles such as pyridine, dibenzofuran, various ethers (resulting in O-dealkylation) and alkanes such as propane, hexane and cyclohexane. Reactions catalysed include hydroxylation, epoxidation, N-oxidation, sulfooxidation, O- and N-dealkylation, bromination and one-electron oxidations. They have little or no activity toward chloride. Mechanistically, the catalytic cycle of unspecific (mono)-peroxygenases combines elements of the "shunt" pathway of cytochrome P-450s (a side activity that utilizes a peroxide in place of dioxygen and NAD[P]H) and the classic heme peroxidase cycle.

Links to other databases:

References:

1.	Ullrich, R., Nuske, J., Scheibner, K., Spantzel, J. and Hofrichter, M. Novel haloperoxidase from the agaric basidiomycete Agrocybe aegerita oxidizes aryl alcohols and aldehydes. Appl. Environ. Microbiol. 70 (2004) 4575–4581. [DOI] [PMID: 15294788]
2.	Ullrich, R. and Hofrichter, M. The haloperoxidase of the agaric fungus Agrocybe aegerita hydroxylates toluene and naphthalene. FEBS Lett. 579 (2005) 6247–6250. [DOI] [PMID: 16253244]
3.	Anh, D.H., Ullrich, R., Benndorf, D., Svatos, A., Muck, A. and Hofrichter, M. The coprophilous mushroom Coprinus radians secretes a haloperoxidase that catalyzes aromatic peroxygenation. Appl. Environ. Microbiol. 73 (2007) 5477–5485. [DOI] [PMID: 17601809]
4.	Ullrich, R., Dolge, C., Kluge, M. and Hofrichter, M. Pyridine as novel substrate for regioselective oxygenation with aromatic peroxygenase from Agrocybe aegerita. FEBS Lett. 582 (2008) 4100–4106. [DOI] [PMID: 19022254]
5.	Aranda, E., Kinne, M., Kluge, M., Ullrich, R. and Hofrichter, M. Conversion of dibenzothiophene by the mushrooms Agrocybe aegerita and Coprinellus radians and their extracellular peroxygenases. Appl. Microbiol. Biotechnol. 82 (2009) 1057–1066. [DOI] [PMID: 19039585]
6.	Kinne, M., Poraj-Kobielska, M., Aranda, E., Ullrich, R., Hammel, K.E., Scheibner, K. and Hofrichter, M. Regioselective preparation of 5-hydroxypropranolol and 4′-hydroxydiclofenac with a fungal peroxygenase. Bioorg. Med. Chem. Lett. 19 (2009) 3085–3087. [DOI] [PMID: 19394224]
7.	Kluge, M., Ullrich, R., Dolge, C., Scheibner, K. and Hofrichter, M. Hydroxylation of naphthalene by aromatic peroxygenase from Agrocybe aegerita proceeds via oxygen transfer from H₂O₂ and intermediary epoxidation. Appl. Microbiol. Biotechnol. 81 (2009) 1071–1076. [DOI] [PMID: 18815784]
8.	Kinne, M., Poraj-Kobielska, M., Ralph, S.A., Ullrich, R., Hofrichter, M. and Hammel, K.E. Oxidative cleavage of diverse ethers by an extracellular fungal peroxygenase. J. Biol. Chem. 284 (2009) 29343–29349. [DOI] [PMID: 19713216]
9.	Pecyna, M.J., Ullrich, R., Bittner, B., Clemens, A., Scheibner, K., Schubert, R. and Hofrichter, M. Molecular characterization of aromatic peroxygenase from Agrocybe aegerita. Appl. Microbiol. Biotechnol. 84 (2009) 885–897. [DOI] [PMID: 19434406]

[EC 1.11.2.1 created 2011]

1.11.2.2

Accepted name:

myeloperoxidase

Reaction:

Cl^- + H₂O₂ + H⁺ = HClO + H₂O

Other name(s):

MPO; verdoperoxidase

Systematic name:

chloride:hydrogen-peroxide oxidoreductase (hypochlorite-forming)

Comments:

Contains calcium and covalently bound heme (proximal ligand histidine). It is present in phagosomes of neutrophils and monocytes, where the hypochlorite produced is strongly bactericidal. It differs from EC 1.11.1.10 chloride peroxidase in its preference for formation of hypochlorite over the chlorination of organic substrates under physiological conditions (pH 5-8). Hypochlorite in turn forms a number of antimicrobial products (Cl₂, chloramines, hydroxyl radical, singlet oxygen). MPO also oxidizes bromide, iodide and thiocyanate. In the absence of halides, it oxidizes phenols and has a moderate peroxygenase activity toward styrene.

Links to other databases:

References:

1.	Agner, K. Myeloperoxidase. Adv. Enzymol. 3 (1943) 137–148.
2.	Harrison, J.E. and Schultz, J. Studies on the chlorinating activity of myeloperoxidase. J. Biol. Chem. 251 (1976) 1371–1374. [PMID: 176150]
3.	Furtmuller, P.G., Burner, U. and Obinger, C. Reaction of myeloperoxidase compound I with chloride, bromide, iodide, and thiocyanate. Biochemistry 37 (1998) 17923–17930. [PMID: 9922160]
4.	Tuynman, A., Spelberg, J.L., Kooter, I.M., Schoemaker, H.E. and Wever, R. Enantioselective epoxidation and carbon-carbon bond cleavage catalyzed by Coprinus cinereus peroxidase and myeloperoxidase. J. Biol. Chem. 275 (2000) 3025–3030. [DOI] [PMID: 10652281]
5.	Klebanoff, S.J. Myeloperoxidase: friend and foe. J. Leukoc. Biol. 77 (2005) 598–625. [DOI] [PMID: 15689384]
6.	Fiedler, T.J., Davey, C.A. and Fenna, R.E. X-ray crystal structure and characterization of halide-binding sites of human myeloperoxidase at 1.8 Å resolution. J. Biol. Chem. 275 (2000) 11964–11971. [DOI] [PMID: 10766826]
7.	Gaut, J.P., Yeh, G.C., Tran, H.D., Byun, J., Henderson, J.P., Richter, G.M., Brennan, M.L., Lusis, A.J., Belaaouaj, A., Hotchkiss, R.S. and Heinecke, J.W. Neutrophils employ the myeloperoxidase system to generate antimicrobial brominating and chlorinating oxidants during sepsis. Proc. Natl. Acad. Sci. USA 98 (2001) 11961–11966. [DOI] [PMID: 11593004]

[EC 1.11.2.2 created 2011]

1.11.2.3

Accepted name:

plant seed peroxygenase

Reaction:

R¹H + R²OOH = R¹OH + R²OH

Other name(s):

plant peroxygenase; soybean peroxygenase

Systematic name:

substrate:hydroperoxide oxidoreductase (RH-hydroxylating or epoxidising)

Comments:

A heme protein with calcium binding motif (caleosin-type). Enzymes of this type include membrane-bound proteins found in seeds of different plants. They catalyse the direct transfer of one oxygen atom from an organic hydroperoxide, which is reduced into its corresponding alcohol to a substrate which will be oxidized. Reactions catalysed include hydroxylation, epoxidation and sulfoxidation. Preferred substrate and co-substrate are unsaturated fatty acids and fatty acid hydroperoxides, respectively. Plant seed peroxygenase is involved in the synthesis of cutin.

Links to other databases:

References:

1.	Ishimaru, A. Purification and characterization of solubilized peroxygenase from microsomes of pea seeds. J. Biol. Chem. 254 (1979) 8427–8433. [PMID: 468835]
2.	Blee, E., Wilcox, A.L., Marnett, L.J. and Schuber, F. Mechanism of reaction of fatty acid hydroperoxides with soybean peroxygenase. J. Biol. Chem. 268 (1993) 1708–1715. [PMID: 8420948]
3.	Hamberg, M. and Hamberg, G. Peroxygenase-catalyzed fatty acid epoxidation in cereal seeds (sequential oxidation of linoleic acid into 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acid). Plant Physiol. 110 (1996) 807–815. [PMID: 12226220]
4.	Lequeu, J., Fauconnier, M.L., Chammai, A., Bronner, R. and Blee, E. Formation of plant cuticle: evidence for the occurrence of the peroxygenase pathway. Plant J. 36 (2003) 155–164. [DOI] [PMID: 14535881]
5.	Hanano, A., Burcklen, M., Flenet, M., Ivancich, A., Louwagie, M., Garin, J. and Blee, E. Plant seed peroxygenase is an original heme-oxygenase with an EF-hand calcium binding motif. J. Biol. Chem. 281 (2006) 33140–33151. [DOI] [PMID: 16956885]

[EC 1.11.2.3 created 2011]

1.11.2.4

Accepted name:

fatty-acid peroxygenase

Reaction:

fatty acid + H₂O₂ = 3- or 2-hydroxy fatty acid + H₂O

Other name(s):

fatty acid hydroxylase (ambiguous); P450 peroxygenase; CYP152A1; P450BS; P450SPα

Systematic name:

fatty acid:hydroperoxide oxidoreductase (RH-hydroxylating)

Comments:

A cytosolic heme-thiolate protein with sequence homology to P-450 monooxygenases. Unlike the latter, it needs neither NAD(P)H, dioxygen nor specific reductases for function. Enzymes of this type are produced by bacteria (e.g. Sphingomonas paucimobilis, Bacillus subtilis). Catalytic turnover rates are high compared with those of monooxygenation reactions as well as peroxide shunt reactions catalysed by the common P-450s. A model substrate is myristate, but other saturated and unsaturated fatty acids are also hydroxylated. Oxidizes the peroxidase substrate 3,3′,5,5′-tetramethylbenzidine (TMB) and peroxygenates aromatic substrates in a fatty-acid-dependent reaction.

Links to other databases:

References:

1.	Matsunaga, I., Yamada, M., Kusunose, E., Nishiuchi, Y., Yano, I. and Ichihara, K. Direct involvement of hydrogen peroxide in bacterial α-hydroxylation of fatty acid. FEBS Lett. 386 (1996) 252–254. [DOI] [PMID: 8647293]
2.	Matsunaga, I., Yamada, M., Kusunose, E., Miki, T. and Ichihara, K. Further characterization of hydrogen peroxide-dependent fatty acid α-hydroxylase from Sphingomonas paucimobilis. J. Biochem. 124 (1998) 105–110. [PMID: 9644252]
3.	Matsunaga, I., Ueda, A., Fujiwara, N., Sumimoto, T. and Ichihara, K. Characterization of the ybdT gene product of Bacillus subtilis: novel fatty acid β-hydroxylating cytochrome P450. Lipids 34 (1999) 841–846. [DOI] [PMID: 10529095]
4.	Imai, Y., Matsunaga, I., Kusunose, E. and Ichihara, K. Unique heme environment at the putative distal region of hydrogen peroxide-dependent fatty acid α-hydroxylase from Sphingomonas paucimobilis (peroxygenase P₄₅₀SPα). J. Biochem. 128 (2000) 189–194. [PMID: 10920253]
5.	Matsunaga, I., Yamada, A., Lee, D.S., Obayashi, E., Fujiwara, N., Kobayashi, K., Ogura, H. and Shiro, Y. Enzymatic reaction of hydrogen peroxide-dependent peroxygenase cytochrome P₄₅₀s: kinetic deuterium isotope effects and analyses by resonance Raman spectroscopy. Biochemistry 41 (2002) 1886–1892. [DOI] [PMID: 11827534]
6.	Lee, D.S., Yamada, A., Sugimoto, H., Matsunaga, I., Ogura, H., Ichihara, K., Adachi, S., Park, S.Y. and Shiro, Y. Substrate recognition and molecular mechanism of fatty acid hydroxylation by cytochrome P₄₅₀ from Bacillus subtilis. Crystallographic, spectroscopic, and mutational studies. J. Biol. Chem. 278 (2003) 9761–9767. [DOI] [PMID: 12519760]
7.	Matsunaga, I. and Shiro, Y. Peroxide-utilizing biocatalysts: structural and functional diversity of heme-containing enzymes. Curr. Opin. Chem. Biol. 8 (2004) 127–132. [DOI] [PMID: 15062772]
8.	Shoji, O., Wiese, C., Fujishiro, T., Shirataki, C., Wunsch, B. and Watanabe, Y. Aromatic C-H bond hydroxylation by P450 peroxygenases: a facile colorimetric assay for monooxygenation activities of enzymes based on Russig’s blue formation. J. Biol. Inorg. Chem. 15 (2010) 1109–1115. [DOI] [PMID: 20490877]

[EC 1.11.2.4 created 2011]

*EC

1.13.12.16

Accepted name:

nitronate monooxygenase

Reaction:

ethylnitronate + O₂ = acetaldehyde + nitrite + other products

Other name(s):

NMO; 2-nitropropane dioxygenase (incorrect)

Systematic name:

nitronate:oxygen 2-oxidoreductase (nitrite-forming)

Comments:

Previously classified as 2-nitropropane dioxygenase (EC 1.13.11.32), but it is now recognized that this was the result of the slow ionization of nitroalkanes to their nitronate (anionic) forms. The enzymes from the fungus Neurospora crassa and the yeast Williopsis saturnus var. mrakii (formerly classified as Hansenula mrakii) contain non-covalently bound FMN as the cofactor. Neither hydrogen peroxide nor superoxide were detected during enzyme turnover. Active towards linear alkyl nitronates of lengths between 2 and 6 carbon atoms and, with lower activity, towards propyl-2-nitronate. The enzyme from N. crassa can also utilize neutral nitroalkanes, but with lower activity.

Links to other databases:

References:

1.	Francis, K., Russell, B. and Gadda, G. Involvement of a flavosemiquinone in the enzymatic oxidation of nitroalkanes catalyzed by 2-nitropropane dioxygenase. J. Biol. Chem. 280 (2005) 5195–5204. [DOI] [PMID: 15582992]
2.	Ha, J.Y., Min, J.Y., Lee, S.K., Kim, H.S., Kim do, J., Kim, K.H., Lee, H.H., Kim, H.K., Yoon, H.J. and Suh, S.W. Crystal structure of 2-nitropropane dioxygenase complexed with FMN and substrate. Identification of the catalytic base. J. Biol. Chem. 281 (2006) 18660–18667. [DOI] [PMID: 16682407]
3.	Gadda, G. and Francis, K. Nitronate monooxygenase, a model for anionic flavin semiquinone intermediates in oxidative catalysis. Arch. Biochem. Biophys. 493 (2010) 53–61. [DOI] [PMID: 19577534]
4.	Francis, K. and Gadda, G. Kinetic evidence for an anion binding pocket in the active site of nitronate monooxygenase. Bioorg. Chem. 37 (2009) 167–172. [DOI] [PMID: 19683782]

[EC 1.13.12.16 created 1984 as EC 1.13.11.32, transferred 2009 to EC 1.13.12.16, modified 2011]

1.13.12.18

Accepted name:

dinoflagellate luciferase

Reaction:

dinoflagellate luciferin + O₂ = oxidized dinoflagellate luciferin + H₂O + hν

For diagram of reaction, click here

Glossary:

dinoflagellate luciferin = (1S,2S,3S)-1-carboxy-3-(2-carboxyethyl)-12-ethyl-2,8,13,18-tetramethyl-17-vinyl-1,2,3,21-tetrahydro-5,7-ethanobilene-a-19(16H),5²-dione

Other name(s):

(dinoflagellate luciferin) luciferase; Gonyaulax luciferase

Systematic name:

dinoflagellate-luciferin:oxygen 13²-oxidoreductase

Comments:

A luciferase from dinoflagellates such as Gonyaulax polyedra, Lingulodinium polyedrum, Noctiluca scintillans, and Pyrocystis lunula. It is a single protein with three luciferase domains. The luciferin is strongly bound by a luciferin binding protein above a pH of 7.

Links to other databases:

BRENDA, EXPASY, KEGG, PDB, CAS registry number: 303183-71-3

References:

1.	Dunlap, J.C. and Hastings, J.W. The biological clock in Gonyaulax controls luciferase activity by regulating turnover. J. Biol. Chem. 256 (1981) 10509–10518. [PMID: 7197271]
2.	Morse, D., Pappenheimer, A.M., Jr. and Hastings, J.W. Role of a luciferin-binding protein in the circadian bioluminescent reaction of Gonyaulax polyedra. J. Biol. Chem. 264 (1989) 11822–11826. [PMID: 2745419]
3.	Bae, Y.M. and Hastings, J.W. Cloning, sequencing and expression of dinoflagellate luciferase DNA from a marine alga, Gonyaulax polyedra. Biochim. Biophys. Acta 1219 (1994) 449–456. [DOI] [PMID: 7918642]
4.	Li, L. Gonyaulax luciferase: gene structure, protein expression, and purification from recombinant sources. Methods Enzymol. 305 (2000) 249–258. [PMID: 10812605]
5.	Morse, D. and Mittag, M. Dinoflagellate luciferin-binding protein. Methods Enzymol. 305 (2000) 258–276. [PMID: 10812606]
6.	Schultz, L.W., Liu, L., Cegielski, M. and Hastings, J.W. Crystal structure of a pH-regulated luciferase catalyzing the bioluminescent oxidation of an open tetrapyrrole. Proc. Natl. Acad. Sci. USA 102 (2005) 1378–1383. [DOI] [PMID: 15665092]

[EC 1.13.12.18 created 2011]

1.14.12.22

Accepted name:

carbazole 1,9a-dioxygenase

Reaction:

9H-carbazole + NAD(P)H + H⁺ + O₂ = 2′-aminobiphenyl-2,3-diol + NAD(P)⁺

Other name(s):

CARDO

Systematic name:

9H-carbazole,NAD(P)H:oxygen oxidoreductase (2,3-hydroxylating)

Comments:

This enzyme catalyses the first reaction in the pathway of carbazole degradation. The enzyme attacks at the 1 and 9a positions of carbazole, resulting in the formation of a highly unstable hemiaminal intermediate that undergoes a spontaneous cleavage and rearomatization, resulting in 2′-aminobiphenyl-2,3-diol. In most bacteria the enzyme is a complex composed of a terminal oxygenase, a ferredoxin, and a ferredoxin reductase. The terminal oxygenase component contains a nonheme iron centre and a Rieske [2Fe-2S] iron-sulfur cluster.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, KEGG, PDB

References:

1.	Nam, J.W., Nojiri, H., Noguchi, H., Uchimura, H., Yoshida, T., Habe, H., Yamane, H. and Omori, T. Purification and characterization of carbazole 1,9a-dioxygenase, a three-component dioxygenase system of Pseudomonas resinovorans strain CA10. Appl. Environ. Microbiol. 68 (2002) 5882–5890. [DOI] [PMID: 12450807]
2.	Gai, Z., Wang, X., Liu, X., Tai, C., Tang, H., He, X., Wu, G., Deng, Z. and Xu, P. The genes coding for the conversion of carbazole to catechol are flanked by IS6100 elements in Sphingomonas sp. strain XLDN2-5. PLoS One 5:e10018 (2010). [DOI] [PMID: 20368802]

[EC 1.14.12.22 created 2010]

*EC

1.14.13.7

Accepted name:

phenol 2-monooxygenase (NADPH)

Reaction:

phenol + NADPH + H⁺ + O₂ = catechol + NADP⁺ + H₂O

For diagram of catechol biosynthesis, click here

Glossary:

o-cresol = 2-cresol = 2-methylphenol

Other name(s):

phenol hydroxylase; phenol o-hydroxylase

Systematic name:

phenol,NADPH:oxygen oxidoreductase (2-hydroxylating)

Comments:

A flavoprotein (FAD). The enzyme from the fungus Trichosporon cutaneum has a broad substrate specificity, and has been reported to catalyse the hydroxylation of a variety of substituted phenols, such as fluoro-, chloro-, amino- and methyl-phenols and also dihydroxybenzenes. cf. EC 1.14.14.20, phenol 2-monooxygenase (FADH₂).

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 37256-84-1

References:

1.	Nakagawa, H. and Takeda, Y. Phenol hydroxylase. Biochim. Biophys. Acta 62 (1962) 423–426. [DOI] [PMID: 14478080]
2.	Neujahr, H.Y. and Gaal, A. Phenol hydroxylase from yeast. Purification and properties of the enzyme from Trichosporon cutaneum. Eur. J. Biochem. 35 (1973) 386–400. [DOI] [PMID: 4146224]
3.	Neujahr, H.Y. and Gaal, A. Phenol hydroxylase from yeast. Sulfhydryl groups in phenol hydroxylase from Trichosporon cutaneum. Eur. J. Biochem. 58 (1975) 351–357. [DOI] [PMID: 810352]

[EC 1.14.13.7 created 1972, modified 2011, modified 2016]

1.14.13.116

Transferred entry:

geranylhydroquinone 3-hydroxylase. Now EC 1.14.14.174, geranylhydroquinone 3-hydroxylase.

[EC 1.14.13.116 created 2010, deleted 2020]

1.14.13.117

Transferred entry:

isoleucine N-monooxygenase, Now EC 1.14.14.39, isoleucine N-monooxygenase

[EC 1.14.13.117 created 2010, deleted 2017]

1.14.13.118

Transferred entry:

valine N-monooxygenase. Now EC 1.14.14.38, valine N-monooxygenase

[EC 1.14.13.118 created 2010, deleted 2017]

1.14.13.119

Transferred entry:

5-epiaristolochene 1,3-dihydroxylase. Now EC 1.14.14.149, 5-epiaristolochene 1,3-dihydroxylase

[EC 1.14.13.119 created 2011, deleted 2018]

1.14.13.120

Transferred entry:

costunolide synthase. Now EC 1.14.14.150, costunolide synthase

[EC 1.14.13.120 created 2011, deleted 2018]

1.14.13.121

Transferred entry:

premnaspirodiene oxygenase. Now EC 1.14.14.151, premnaspirodiene oxygenase

[EC 1.14.13.121 created 2011, deleted 2018]

*EC

1.14.15.7

Accepted name:

choline monooxygenase

Reaction:

choline + O₂ + 2 reduced ferredoxin + 2 H⁺ = betaine aldehyde hydrate + H₂O + 2 oxidized ferredoxin

Glossary:

betaine = glycine betaine = N,N,N-trimethylglycine = N,N,N-trimethylammonioacetate
betaine aldehyde = N,N,N-trimethyl-2-oxoethylammonium
choline = (2-hydroxyethyl)trimethylammonium

Systematic name:

choline,reduced-ferredoxin:oxygen oxidoreductase

Comments:

The spinach enzyme, which is located in the chloroplast, contains a Rieske-type [2Fe-2S] cluster, and probably also a mononuclear Fe centre. Requires Mg²⁺. Catalyses the first step of glycine betaine synthesis. In many bacteria, plants and animals, betaine is synthesized in two steps: (1) choline to betaine aldehyde and (2) betaine aldehyde to betaine. Different enzymes are involved in the first reaction. In plants, the reaction is catalysed by this enzyme whereas in animals and many bacteria it is catalysed by either membrane-bound EC 1.1.99.1 (choline dehydrogenase) or soluble EC 1.1.3.17 (choline oxidase) [7]. The enzyme involved in the second step, EC 1.2.1.8 (betaine-aldehyde dehydrogenase), appears to be the same in plants, animals and bacteria. In some bacteria, betaine is synthesized from glycine through the actions of EC 2.1.1.156 (glycine/sarcosine N-methyltransferase) and EC 2.1.1.157 (sarcosine/dimethylglycine N-methyltransferase).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 118390-76-4

References:

1.	Brouquisse, R., Weigel, P., Rhodes, D., Yocum, C.F. and Hanson, A.D. Evidence for a ferredoxin-dependent choline monooxygenase from spinach chloroplast stroma. Plant Physiol. 90 (1989) 322–329. [PMID: 16666757]
2.	Burnet, M., Lafontaine, P.J. and Hanson, A.D. Assay, purification, and partial characterization of choline monooxygenase from spinach. Plant Physiol. 108 (1995) 581–588. [PMID: 12228495]
3.	Rathinasabapathi, B., Burnet, M., Russell, B.L., Gage, D.A., Liao, P., Nye, G.J., Scott, P., Golbeck, J.H. and Hanson, A.D. Choline monooxygenase, an unusual iron-sulfur enzyme catalyzing the first step of glycine betaine synthesis in plants: Prosthetic group characterization and cDNA cloning. Proc. Natl. Acad. Sci. USA 94 (1997) 3454–3458. [DOI] [PMID: 9096415]
4.	Russell, B.L., Rathinasabapathi, B. and Hanson, A.D. Osmotic stress induces expression of choline monooxygenase in sugar beet and amaranth. Plant Physiol. 116 (1998) 859–865. [PMID: 9489025]
5.	Nuccio, M.L., Russell, B.L., Nolte, K.D., Rathinasabapathi, B., Gage, D.A. and Hanson, A.D. Glycine betaine synthesis in transgenic tobacco expressing choline monooxygenase is limited by the endogenous choline supply. Plant J. 16 (1998) 101–110.
6.	Nuccio, M.L., Russell, B.L., Nolte, K.D., Rathinasabapathi, B., Gage, D.A. and Hanson, A.D. The endogenous choline supply limits glycine betaine synthesis in transgenic tobacco expressing choline. Plant J. 16 (1998) 487–496. [DOI] [PMID: 9881168]
7.	Waditee, R., Tanaka, Y., Aoki, K., Hibino, T., Jikuya, H., Takano, J., Takabe, T. and Takabe, T. Isolation and functional characterization of N-methyltransferases that catalyze betaine synthesis from glycine in a halotolerant photosynthetic organism Aphanothece halophytica. J. Biol. Chem. 278 (2003) 4932–4942. [DOI] [PMID: 12466265]

[EC 1.14.15.7 created 2001, modified 2002 (EC 1.14.14.4 created 2000, incorporated 2002), modified 2005, modified 2011]

1.14.21.8

Transferred entry:

pseudobaptigenin synthase. Now EC 1.14.19.63, pseudobaptigenin synthase.

[EC 1.14.21.8 created 2011, deleted 2018]

1.17.5.2

Accepted name:

caffeine dehydrogenase

Reaction:

caffeine + ubiquinone + H₂O = 1,3,7-trimethylurate + ubiquinol

Glossary:

caffeine = 1,3,7-trimethylxanthine

Systematic name:

caffeine:ubiquinone oxidoreductase

Comments:

This enzyme, characterized from the soil bacterium Pseudomonas sp. CBB1, catalyses the incorporation of an oxygen atom originating from a water molecule into position C-8 of caffeine. It can also use theobromine as substrate. The enzyme utilizes short-tail ubiquinones as the preferred electron acceptor.

Links to other databases:

References:

1.	Yu, C.L., Kale, Y., Gopishetty, S., Louie, T.M. and Subramanian, M. A novel caffeine dehydrogenase in Pseudomonas sp. strain CBB1 oxidizes caffeine to trimethyluric acid. J. Bacteriol. 190 (2008) 772–776. [DOI] [PMID: 17981969]

[EC 1.17.5.2 created 2010]

*EC

1.17.99.1

Transferred entry:

4-methylphenol dehydrogenase (hydroxylating). Now EC 1.17.9.1, 4-methylphenol dehydrogenase (hydroxylating)

[EC 1.17.99.1 created 1983, modified 2001, modified 2011, modified 2015, deleted 2018]

2.1.1.29

Transferred entry:

tRNA (cytosine-5-)-methyltransferase. Now covered by EC 2.1.1.202 [multisite-specific tRNA:(cytosine-C⁵)-methyltransferase], EC 2.1.1.203 [tRNA (cytosine³⁴-C⁵)-methyltransferase] and EC 2.1.1.204 [RNA (cytosine³⁸-C⁵)-methyltransferase].

[EC 2.1.1.29 created 1972, deleted 2011]

*EC

2.1.1.64

Accepted name:

3-demethylubiquinol 3-O-methyltransferase

Reaction:

S-adenosyl-L-methionine + 3-demethylubiquinol-n = S-adenosyl-L-homocysteine + ubiquinol-n

For diagram of ubiquinol biosynthesis, click here

Glossary:

3-demethylubiquinol-n = 3-hydroxy-2-methoxy-5-methyl-6-(all-trans-polyprenyl)-1,4-benzoquinol

Other name(s):

5-demethylubiquinone-9 methyltransferase; OMHMB-methyltransferase; 2-octaprenyl-3-methyl-5-hydroxy-6-methoxy-1,4-benzoquinone methyltransferase; S-adenosyl-L-methionine:2-octaprenyl-3-methyl-5-hydroxy-6-methoxy-1,4-benzoquinone-O-methyltransferase; COQ3 (gene name); Coq3 O-methyltransferase; 3-demethylubiquinone-9 3-methyltransferase; ubiG (gene name, ambiguous)

Systematic name:

S-adenosyl-L-methionine:3-hydroxy-2-methoxy-5-methyl-6-(all-trans-polyprenyl)-1,4-benzoquinol 3-O-methyltransferase

Comments:

This enzyme is involved in ubiquinone biosynthesis. Ubiquinones from different organisms have a different number of prenyl units (for example, ubiquinone-6 in Saccharomyces, ubiquinone-9 in rat and ubiquinone-10 in human), and thus the natural substrate for the enzymes from different organisms has a different number of prenyl units. However, the enzyme usually shows a low degree of specificity regarding the number of prenyl units. For example, the human COQ3 enzyme can restore biosynthesis of ubiquinone-6 in coq3 deletion mutants of yeast [3]. The enzymes from yeast, Escherichia coli and rat also catalyse the methylation of 3,4-dihydroxy-5-all-trans-polyprenylbenzoate [3] (a reaction that is classified as EC 2.1.1.114, polyprenyldihydroxybenzoate methyltransferase).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 63774-48-1

References:

1.	Houser, R.M. and Olson, R.E. 5-Demethylubiquinone-9-methyltransferase from rat liver mitochondria. Characterization, localization, and solubilization. J. Biol. Chem. 252 (1977) 4017–4021. [PMID: 863914]
2.	Leppik, R.A., Stroobant, P., Shineberg, B., Young, I.G. and Gibson, F. Membrane-associated reactions in ubiquinone biosynthesis. 2-Octaprenyl-3-methyl-5-hydroxy-6-methoxy-1,4-benzoquinone methyltransferase. Biochim. Biophys. Acta 428 (1976) 146–156. [DOI] [PMID: 769831]
3.	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]
4.	Jonassen, T. and Clarke, C.F. Isolation and functional expression of human COQ3, a gene encoding a methyltransferase required for ubiquinone biosynthesis. J. Biol. Chem. 275 (2000) 12381–12387. [DOI] [PMID: 10777520]

[EC 2.1.1.64 created 1982, modified 2011]

*EC

2.1.1.114

Accepted name:

polyprenyldihydroxybenzoate methyltransferase

Reaction:

S-adenosyl-L-methionine + 3,4-dihydroxy-5-all-trans-polyprenylbenzoate = S-adenosyl-L-homocysteine + 3-methoxy-4-hydroxy-5-all-trans-polyprenylbenzoate

For diagram of ubiquinol biosynthesis, click here

Other name(s):

3,4-dihydroxy-5-hexaprenylbenzoate methyltransferase; dihydroxyhexaprenylbenzoate methyltransferase; COQ3 (gene name); Coq3 O-methyltransferase; DHHB O-methyltransferase

Systematic name:

S-adenosyl-L-methionine:3,4-dihydroxy-5-all-trans-polyprenylbenzoate 3-O-methyltransferase

Comments:

This enzyme is involved in ubiquinone biosynthesis. Ubiquinones from different organisms have a different number of prenyl units (for example, ubiquinone-6 in Saccharomyces, ubiquinone-9 in rat and ubiquinone-10 in human), and thus the natural substrate for the enzymes from different organisms has a different number of prenyl units. However, the enzyme usually shows a low degree of specificity regarding the number of prenyl units. For example, the human COQ3 enzyme can restore biosynthesis of ubiquinone-6 in coq3 deletion mutants of yeast [3]. The enzymes from yeast and rat also catalyse the methylation of 3-demethylubiquinol-6 and 3-demethylubiquinol-9, respectively [2] (this activity is classified as EC 2.1.1.64, 3-demethylubiquinol 3-O-methyltransferase).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 139569-31-6

References:

1.	Clarke, C.F., Williams, W., Teruya, J.H. Ubiquinone biosynthesis in Saccharomyces cerevisiae. Isolation and sequence of COQ3, the 3,4-dihydroxy-5-hexaprenylbenzoate methyltransferase gene. J. Biol. Chem. 266 (1991) 16636–16641. [PMID: 1885593]
2.	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]
3.	Jonassen, T. and Clarke, C.F. Isolation and functional expression of human COQ3, a gene encoding a methyltransferase required for ubiquinone biosynthesis. J. Biol. Chem. 275 (2000) 12381–12387. [DOI] [PMID: 10777520]
4.	Xing, L., Zhu, Y., Fang, P., Wang, J., Zeng, F., Li, X., Teng, M. and Li, X. Crystallization and preliminary crystallographic studies of UbiG, an O-methyltransferase from Escherichia coli. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 67 (2011) 727–729. [DOI] [PMID: 21636923]

[EC 2.1.1.114 created 1999]

2.1.1.195

Accepted name:

cobalt-precorrin-5B (C1)-methyltransferase

Reaction:

S-adenosyl-L-methionine + cobalt-precorrin-5B = S-adenosyl-L-homocysteine + cobalt-precorrin-6A

For diagram of anaerobic corrin biosynthesis (part 1), click here

Glossary:

cobalt-precorrin-6A = cobalt-precorrin-6x

Other name(s):

cobalt-precorrin-6A synthase; CbiD

Systematic name:

S-adenosyl-L-methionine:cobalt-precorrin-5B C¹-methyltransferase

Comments:

This enzyme catalyses the C-1 methylation of cobalt-precorrin-5B in the anaerobic (early cobalt insertion) pathway of adenosylcobalamin biosynthesis. See EC 2.1.1.152, precorrin-6A synthase (deacetylating), for the C¹-methyltransferase that participates in the aerobic cobalamin biosynthesis pathway.

Links to other databases:

References:

1.	Roper, J.M., Raux, E., Brindley, A.A., Schubert, H.L., Gharbia, S.E., Shah, H.N. and Warren, M.J. The enigma of cobalamin (Vitamin B₁₂) biosynthesis in Porphyromonas gingivalis. Identification and characterization of a functional corrin pathway. J. Biol. Chem. 275 (2000) 40316–40323. [DOI] [PMID: 11007789]
2.	Roessner, C.A., Williams, H.J. and Scott, A.I. Genetically engineered production of 1-desmethylcobyrinic acid, 1-desmethylcobyrinic acid a,c-diamide, and cobyrinic acid a,c-diamide in Escherichia coli implies a role for CbiD in C-1 methylation in the anaerobic pathway to cobalamin. J. Biol. Chem. 280 (2005) 16748–16753. [DOI] [PMID: 15741157]
3.	Moore, S.J., Lawrence, A.D., Biedendieck, R., Deery, E., Frank, S., Howard, M.J., Rigby, S.E. and Warren, M.J. Elucidation of the anaerobic pathway for the corrin component of cobalamin (vitamin B₁₂). Proc. Natl. Acad. Sci. USA 110 (2013) 14906–14911. [DOI] [PMID: 23922391]

[EC 2.1.1.195 created 2010]

2.1.1.196

Accepted name:

cobalt-precorrin-6B (C15)-methyltransferase [decarboxylating]

Reaction:

S-adenosyl-L-methionine + cobalt-precorrin-6B = S-adenosyl-L-homocysteine + cobalt-precorrin-7 + CO₂

For diagram of anaerobic corrin biosynthesis (part 2), click here

Other name(s):

cbiT (gene name); S-adenosyl-L-methionine:precorrin-7 C¹⁵-methyltransferase (C-12-decarboxylating); cobalt-precorrin-7 (C15)-methyltransferase [decarboxylating]

Systematic name:

S-adenosyl-L-methionine:precorrin-6B C¹⁵-methyltransferase (C-12-decarboxylating)

Comments:

This enzyme, which participates in the anaerobic (early cobalt insertion) adenosylcobalamin biosynthesis pathway, catalyses both methylation at C-15 and decarboxylation of the C-12 acetate side chain of cobalt-precorrin-6B. The equivalent activity in the aerobic adenosylcobalamin biosynthesis pathway is catalysed by the bifunctional enzyme EC 2.1.1.132, precorrin-6B C5,15-methyltransferase (decarboxylating).

Links to other databases:

References:

1.	Keller, J.P., Smith, P.M., Benach, J., Christendat, D., deTitta, G.T. and Hunt, J.F. The crystal structure of MT0146/CbiT suggests that the putative precorrin-8w decarboxylase is a methyltransferase. Structure 10 (2002) 1475–1487. [DOI] [PMID: 12429089]
2.	Santander, P.J., Kajiwara, Y., Williams, H.J. and Scott, A.I. Structural characterization of novel cobalt corrinoids synthesized by enzymes of the vitamin B₁₂ anaerobic pathway. Bioorg. Med. Chem. 14 (2006) 724–731. [DOI] [PMID: 16198574]
3.	Moore, S.J., Lawrence, A.D., Biedendieck, R., Deery, E., Frank, S., Howard, M.J., Rigby, S.E. and Warren, M.J. Elucidation of the anaerobic pathway for the corrin component of cobalamin (vitamin B₁₂). Proc. Natl. Acad. Sci. USA 110 (2013) 14906–14911. [DOI] [PMID: 23922391]

[EC 2.1.1.196 created 2010, modified 2013]

2.1.1.197

Accepted name:

malonyl-[acyl-carrier protein] O-methyltransferase

Reaction:

S-adenosyl-L-methionine + malonyl-[acyl-carrier protein] = S-adenosyl-L-homocysteine + malonyl-[acyl-carrier protein] methyl ester

Other name(s):

BioC

Systematic name:

S-adenosyl-L-methionine:malonyl-[acyl-carrier protein] O-methyltransferase

Comments:

Involved in an early step of biotin biosynthesis in Gram-negative bacteria. This enzyme catalyses the transfer of a methyl group to the ω-carboxyl group of malonyl-[acyl-carrier protein] forming a methyl ester. The methyl ester is recognized by the fatty acid synthetic enzymes, which process it via the fatty acid elongation cycle to give pimelyl-[acyl-carrier-protein] methyl ester [5]. While the enzyme can also accept malonyl-CoA, it has a much higher activity with malonyl-[acyl-carrier protein] [6]

Links to other databases:

References:

1.	Del Campillo-Campbell, A., Kayajanian, G., Campbell, A. and Adhya, S. Biotin-requiring mutants of Escherichia coli K-12. J. Bacteriol. 94 (1967) 2065–2066. [PMID: 4864413]
2.	Rolfe, B. and Eisenberg, M.A. Genetic and biochemical analysis of the biotin loci of Escherichia coli K-12. J. Bacteriol. 96 (1968) 515–524. [PMID: 4877129]
3.	Otsuka, A.J., Buoncristiani, M.R., Howard, P.K., Flamm, J., Johnson, C., Yamamoto, R., Uchida, K., Cook, C., Ruppert, J. and Matsuzaki, J. The Escherichia coli biotin biosynthetic enzyme sequences predicted from the nucleotide sequence of the bio operon. J. Biol. Chem. 263 (1988) 19577–19585. [PMID: 3058702]
4.	Cleary, P.P. and Campbell, A. Deletion and complementation analysis of biotin gene cluster of Escherichia coli. J. Bacteriol. 112 (1972) 830–839. [PMID: 4563978]
5.	Lin, S., Hanson, R.E. and Cronan, J.E. Biotin synthesis begins by hijacking the fatty acid synthetic pathway. Nat. Chem. Biol. 6 (2010) 682–688. [DOI] [PMID: 20693992]
6.	Lin, S. and Cronan, J.E. The BioC O-methyltransferase catalyzes methyl esterification of malonyl-acyl carrier protein, an essential step in biotin synthesis. J. Biol. Chem. 287 (2012) 37010–37020. [DOI] [PMID: 22965231]

[EC 2.1.1.197 created 2010, modified 2013]

2.1.1.198

Accepted name:

16S rRNA (cytidine¹⁴⁰²-2′-O)-methyltransferase

Reaction:

S-adenosyl-L-methionine + cytidine¹⁴⁰² in 16S rRNA = S-adenosyl-L-homocysteine + 2′-O-methylcytidine¹⁴⁰² in 16S rRNA

Other name(s):

RsmI; YraL

Systematic name:

S-adenosyl-L-methionine:16S rRNA (cytidine¹⁴⁰²-2′-O)-methyltransferase

Comments:

RsmI catalyses the 2′-O-methylation of cytidine¹⁴⁰² and RsmH (EC 2.1.1.199) catalyses the N⁴-methylation of cytidine¹⁴⁰² in 16S rRNA. Both methylations are necessary for efficient translation initiation at the UUG and GUG codons.

Links to other databases:

References:

1.	Kimura, S. and Suzuki, T. Fine-tuning of the ribosomal decoding center by conserved methyl-modifications in the Escherichia coli 16S rRNA. Nucleic Acids Res. 38 (2010) 1341–1352. [DOI] [PMID: 19965768]

[EC 2.1.1.198 created 2010]

2.1.1.199

Accepted name:

16S rRNA (cytosine¹⁴⁰²-N⁴)-methyltransferase

Reaction:

S-adenosyl-L-methionine + cytosine¹⁴⁰² in 16S rRNA = S-adenosyl-L-homocysteine + N⁴-methylcytosine¹⁴⁰² in 16S rRNA

Other name(s):

RsmH; MraW

Systematic name:

S-adenosyl-L-methionine:16S rRNA (cytosine¹⁴⁰²-N⁴)-methyltransferase

Comments:

RsmH catalyses the N⁴-methylation of cytosine¹⁴⁰² and RsmI (EC 2.1.1.198) catalyses the 2′-O-methylation of cytosine¹⁴⁰² in 16S rRNA. Both methylations are necessary for efficient translation initiation at the UUG and GUG codons.

Links to other databases:

References:

1.	Kimura, S. and Suzuki, T. Fine-tuning of the ribosomal decoding center by conserved methyl-modifications in the Escherichia coli 16S rRNA. Nucleic Acids Res. 38 (2010) 1341–1352. [DOI] [PMID: 19965768]

[EC 2.1.1.199 created 2010]

2.1.1.200

Accepted name:

tRNA (cytidine³²/uridine³²-2′-O)-methyltransferase

Reaction:

(1) S-adenosyl-L-methionine + cytidine³² in tRNA = S-adenosyl-L-homocysteine + 2′-O-methylcytidine³² in tRNA
(2) S-adenosyl-L-methionine + uridine³² in tRNA = S-adenosyl-L-homocysteine + 2′-O-methyluridine³² in tRNA

Other name(s):

YfhQ; tRNA:Cm32/Um32 methyltransferase; TrMet(Xm32); TrmJ

Systematic name:

S-adenosyl-L-methionine:tRNA (cytidine³²/uridine³²-2′-O)-methyltransferase

Comments:

In Escherichia coli YfhQ is the only methyltransferase responsible for the formation of 2′-O-methylcytidine³² in tRNA. No methylation of cytosine³⁴ in tRNA^Leu(CAA). In vitro the enzyme 2-O-methylates cytidine³² of tRNA^Ser¹ and uridine³² of tRNA^Gln2.

Links to other databases:

References:

1.	Purta, E., van Vliet, F., Tkaczuk, K.L., Dunin-Horkawicz, S., Mori, H., Droogmans, L. and Bujnicki, J.M. The yfhQ gene of Escherichia coli encodes a tRNA:Cm32/Um32 methyltransferase. BMC Mol. Biol. 7:23 (2006). [DOI] [PMID: 16848900]

[EC 2.1.1.200 created 2011]

2.1.1.201

Accepted name:

2-methoxy-6-polyprenyl-1,4-benzoquinol methylase

Reaction:

S-adenosyl-L-methionine + 2-methoxy-6-all-trans-polyprenyl-1,4-benzoquinol = S-adenosyl-L-homocysteine + 6-methoxy-3-methyl-2-all-trans-polyprenyl-1,4-benzoquinol

For diagram of ubiquinol biosynthesis, click here

Other name(s):

ubiE (gene name, ambiguous)

Systematic name:

S-adenosyl-L-methionine:2-methoxy-6-all-trans-polyprenyl-1,4-benzoquinol 5-C-methyltransferase

Comments:

This enzyme is involved in ubiquinone biosynthesis. Ubiquinones from different organisms have a different number of prenyl units (for example, ubiquinone-6 in Saccharomyces, ubiquinone-9 in rat and ubiquinone-10 in human), and thus the natural substrate for the enzymes from different organisms has a different number of prenyl units. However, the enzyme usually shows a low degree of specificity regarding the number of prenyl units. For example, when the COQ5 gene from Saccharomyces cerevisiae is introduced into Escherichia coli, it complements the respiratory deficiency of an ubiE mutant [3]. The bifunctional enzyme from Escherichia coli also catalyses the methylation of demethylmenaquinol-8 (this activity is classified as EC 2.1.1.163) [1].

Links to other databases:

References:

1.	Lee, P.T., Hsu, A.Y., Ha, H.T. and Clarke, C.F. A C-methyltransferase involved in both ubiquinone and menaquinone biosynthesis: isolation and identification of the Escherichia coli ubiE gene. J. Bacteriol. 179 (1997) 1748–1754. [DOI] [PMID: 9045837]
2.	Young, I.G., McCann, L.M., Stroobant, P. and Gibson, F. Characterization and genetic analysis of mutant strains of Escherichia coli K-12 accumulating the biquinone precursors 2-octaprenyl-6-methoxy-1,4-benzoquinone and 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone. J. Bacteriol. 105 (1971) 769–778. [PMID: 4323297]
3.	Dibrov, E., Robinson, K.M. and Lemire, B.D. The COQ5 gene encodes a yeast mitochondrial protein necessary for ubiquinone biosynthesis and the assembly of the respiratory chain. J. Biol. Chem. 272 (1997) 9175–9181. [DOI] [PMID: 9083048]
4.	Barkovich, R.J., Shtanko, A., Shepherd, J.A., Lee, P.T., Myles, D.C., Tzagoloff, A. and Clarke, C.F. Characterization of the COQ5 gene from Saccharomyces cerevisiae. Evidence for a C-methyltransferase in ubiquinone biosynthesis. J. Biol. Chem. 272 (1997) 9182–9188. [DOI] [PMID: 9083049]

[EC 2.1.1.201 created 2011]

2.1.1.202

Accepted name:

multisite-specific tRNA:(cytosine-C⁵)-methyltransferase

Reaction:

(1) S-adenosyl-L-methionine + cytosine³⁴ in tRNA precursor = S-adenosyl-L-homocysteine + 5-methylcytosine³⁴ in tRNA precursor
(2) S-adenosyl-L-methionine + cytosine⁴⁰ in tRNA precursor = S-adenosyl-L-homocysteine + 5-methylcytosine⁴⁰ in tRNA precursor
(3) S-adenosyl-L-methionine + cytosine⁴⁸ in tRNA = S-adenosyl-L-homocysteine + 5-methylcytosine⁴⁸ in tRNA
(4) S-adenosyl-L-methionine + cytosine⁴⁹ in tRNA = S-adenosyl-L-homocysteine + 5-methylcytosine⁴⁹ in tRNA

Other name(s):

multisite-specific tRNA:m5C-methyltransferase; TRM4 (gene name, gene corresponding to ORF YBL024w)

Systematic name:

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

Comments:

The enzyme from Saccharomyces cerevisiae is responsible for complete 5-methylcytosine methylations of yeast tRNA. The incidence of modification depends on the cytosine position in tRNA. At positions 34 and 40, 5-methylcytosine is found only in two yeast tRNAs (tRNA^Leu(CUA) and tRNA^Phe(GAA), respectively), whereas most other elongator yeast tRNAs bear either 5-methylcytosine⁴⁸ or 5-methylcytosine⁴⁹, but never both in the same tRNA molecule [1]. The formation of 5-methylcytosine³⁴ and 5-methylcytosine⁴⁰ is a strictly intron-dependent process, whereas the formation of 5-methylcytosine⁴⁸ and 5-methylcytosine⁴⁹ is an intron-independent process [2,3].

Links to other databases:

References:

1.	Motorin, Y. and Grosjean, H. Multisite-specific tRNA:m5C-methyltransferase (Trm4) in yeast Saccharomyces cerevisiae: identification of the gene and substrate specificity of the enzyme. RNA 5 (1999) 1105–1118. [PMID: 10445884]
2.	Jiang, H.Q., Motorin, Y., Jin, Y.X. and Grosjean, H. Pleiotropic effects of intron removal on base modification pattern of yeast tRNA^Phe: an in vitro study. Nucleic Acids Res. 25 (1997) 2694–2701. [DOI] [PMID: 9207014]
3.	Strobel, M.C. and Abelson, J. Effect of intron mutations on processing and function of Saccharomyces cerevisiae SUP53 tRNA in vitro and in vivo. Mol. Cell Biol. 6 (1986) 2663–2673. [DOI] [PMID: 3537724]
4.	Walbott, H., Husson, C., Auxilien, S. and Golinelli-Pimpaneau, B. Cysteine of sequence motif VI is essential for nucleophilic catalysis by yeast tRNA m⁵C methyltransferase. RNA 13 (2007) 967–973. [DOI] [PMID: 17475914]

[EC 2.1.1.202 created 1976 as EC 2.1.1.29, part transferred 2011 to EC 2.1.1.202]

2.1.1.203

Accepted name:

tRNA (cytosine³⁴-C⁵)-methyltransferase

Reaction:

S-adenosyl-L-methionine + cytosine³⁴ in tRNA precursor = S-adenosyl-L-homocysteine + 5-methylcytosine³⁴ in tRNA precursor

Other name(s):

hTrm4 Mtase; hTrm4 methyltransferase; hTrm4 (gene name); tRNA:m5C-methyltransferase (ambiguous)

Systematic name:

S-adenosyl-L-methionine:tRNA (cytosine³⁴-C⁵)-methyltransferase

Comments:

The human enzyme is specific for C⁵-methylation of cytosine³⁴ in tRNA precursors. The intron in the human pre-tRNA^Leu(CAA) is indispensable for the C⁵-methylation of cytosine in the first position of the anticodon. It is not able to form 5-methylcytosine at positions 48 and 49 of human and yeast tRNA precursors [1].

Links to other databases:

References:

Brzezicha, B., Schmidt, M., Makalowska, I., Jarmolowski, A., Pienkowska, J. and Szweykowska-Kulinska, Z. Identification of human tRNA:m⁵C methyltransferase catalysing intron-dependent m⁵C formation in the first position of the anticodon of the pre-tRNA Leu (CAA). Nucleic Acids Res. 34 (2006) 6034–6043. [DOI] [PMID: 17071714]

[EC 2.1.1.203 created 1976 as EC 2.1.1.29, part transferred 2011 to EC 2.1.1.203]

2.1.1.204

Accepted name:

tRNA (cytosine³⁸-C⁵)-methyltransferase

Reaction:

S-adenosyl-L-methionine + cytosine³⁸ in tRNA = S-adenosyl-L-homocysteine + 5-methylcytosine³⁸ in tRNA

Other name(s):

hDNMT2 (gene name); DNMT2 (gene name); TRDMT1 (gene name)

Systematic name:

S-adenosyl-L-methionine:tRNA (cytosine³⁸-C⁵)-methyltransferase

Comments:

The eukaryotic enzyme catalyses methylation of cytosine³⁸ in the anti-codon loop of tRNA^Asp(GTC), tRNA^Val(AAC) and tRNA^Gly(GCC). Methylation by Dnmt2 protects tRNAs against stress-induced cleavage by ribonuclease [3].

Links to other databases:

References:

1.	Goll, M.G., Kirpekar, F., Maggert, K.A., Yoder, J.A., Hsieh, C.L., Zhang, X., Golic, K.G., Jacobsen, S.E. and Bestor, T.H. Methylation of tRNA^Asp by the DNA methyltransferase homolog Dnmt2. Science 311 (2006) 395–398. [DOI] [PMID: 16424344]
2.	Jurkowski, T.P., Meusburger, M., Phalke, S., Helm, M., Nellen, W., Reuter, G. and Jeltsch, A. Human DNMT2 methylates tRNA(Asp) molecules using a DNA methyltransferase-like catalytic mechanism. RNA 14 (2008) 1663–1670. [DOI] [PMID: 18567810]
3.	Schaefer, M., Pollex, T., Hanna, K., Tuorto, F., Meusburger, M., Helm, M. and Lyko, F. RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. Genes Dev. 24 (2010) 1590–1595. [DOI] [PMID: 20679393]

[EC 2.1.1.204 created 1976 as EC 2.1.1.29, part transferred 2011 to EC 2.1.1.204]

2.1.1.205

Accepted name:

tRNA (cytidine³²/guanosine³⁴-2′-O)-methyltransferase

Reaction:

S-adenosyl-L-methionine + cytidine³²/guanosine³⁴ in tRNA = S-adenosyl-L-homocysteine + 2′-O-methylcytidine³²/2′-O-methylguanosine³⁴ in tRNA

Other name(s):

Trm7p

Systematic name:

S-adenosyl-L-methionine:tRNA (cytidine³²/guanosine³⁴-2′-O)-methyltransferase

Comments:

The enzyme from Saccharomyces cerevisiae catalyses the formation of 2′-O-methylnucleotides at positions 32 and 34 of the yeast tRNA^Phe, tRNA^Trp and, possibly, tRNA^Leu.

Links to other databases:

References:

1.	Pintard, L., Lecointe, F., Bujnicki, J.M., Bonnerot, C., Grosjean, H. and Lapeyre, B. Trm7p catalyses the formation of two 2′-O-methylriboses in yeast tRNA anticodon loop. EMBO J. 21 (2002) 1811–1820. [DOI] [PMID: 11927565]

[EC 2.1.1.205 created 2011]

2.1.1.206

Accepted name:

tRNA (cytidine⁵⁶-2′-O)-methyltransferase

Reaction:

S-adenosyl-L-methionine + cytidine⁵⁶ in tRNA = S-adenosyl-L-homocysteine + 2′-O-methylcytidine⁵⁶ in tRNA

Other name(s):

aTrm56; tRNA ribose 2′-O-methyltransferase aTrm56; PAB1040 (gene name)

Systematic name:

S-adenosyl-L-methionine:tRNA (cytidine⁵⁶-2′-O)-methyltransferase

Comments:

The archaeal enzyme specifically catalyses the S-adenosyl-L-methionine dependent 2′-O-ribose methylation of cytidine at position 56 in tRNA transcripts.

Links to other databases:

References:

1.	Renalier, M.H., Joseph, N., Gaspin, C., Thebault, P. and Mougin, A. The Cm56 tRNA modification in archaea is catalyzed either by a specific 2′-O-methylase, or a C/D sRNP. RNA 11 (2005) 1051–1063. [DOI] [PMID: 15987815]
2.	Kuratani, M., Bessho, Y., Nishimoto, M., Grosjean, H. and Yokoyama, S. Crystal structure and mutational study of a unique SpoU family archaeal methylase that forms 2′-O-methylcytidine at position 56 of tRNA. J. Mol. Biol. 375 (2008) 1064–1075. [DOI] [PMID: 18068186]

[EC 2.1.1.206 created 2011]

2.3.1.192

Accepted name:

glycine N-phenylacetyltransferase

Reaction:

phenylacetyl-CoA + glycine = CoA + phenylacetylglycine

Other name(s):

arylacetyl-CoA N-acyltransferase; arylacetyltransferase; GAT (gene name)

Systematic name:

phenylacetyl-CoA:glycine N-phenylacetyltransferase

Comments:

Not identical with EC 2.3.1.13 (glycine N-acyltransferase). This enzyme was purified from bovine liver mitochondria. L-asparagine, L-glutamine and L-arginine are alternative substrates to glycine, but have higher K_m values.

Links to other databases:

References:

1.	Nandi, D.L., Lucas, S.V. and Webster, L.T. Benzoyl-coenzyme A:glycine N-acyltransferase and phenylacetyl-coenzyme A:glycine N-acyltransferase from bovine liver mitochondria. Purification and characterization. J. Biol. Chem. 254 (1979) 7230–7237. [PMID: 457678]
2.	Kelley, M. and Vessey, D.A. The effects of ions on the conjugation of xenobiotics by the aralkyl-CoA and arylacetyl-CoA N-acyltransferases from bovine liver mitochondria. J. Biochem. Toxicol. 5 (1990) 125–135. [DOI] [PMID: 2283662]
3.	Vessey, D.A. and Lau, E. Determination of the sequence of the arylacetyl acyl-CoA:amino acid N-acyltransferase from bovine liver mitochondria and its homology to the aralkyl acyl-CoA:amino acid N-acyltransferase. J. Biochem. Mol. Toxicol. 12 (1998) 275–279. [DOI] [PMID: 9664233]

[EC 2.3.1.192 created 2010]

2.3.1.193

Accepted name:

tRNA^Met cytidine acetyltransferase

Reaction:

[elongator tRNA^Met]-cytidine³⁴ + ATP + acetyl-CoA + H₂O = CoA + [elongator tRNA^Met]-N⁴-acetylcytidine³⁴ + ADP + phosphate

Other name(s):

YpfI; TmcA

Systematic name:

acetyl-CoA:[elongator tRNA^Met]-cytidine³⁴ N⁴-acetyltransferase (ATP-hydrolysing)

Comments:

The enzyme acetylates the wobble base cytidine³⁴ of the CAU anticodon of elongation-specific tRNA^Met. Escherichia coli TmcA strictly discriminates elongator tRNA^Met from tRNA^Ile, which is structurally similar and has the same anticodon loop, mainly by recognizing the C²⁷-G⁴³ pair in the anticodon stem. The enzyme can use GTP in place of ATP for formation of N⁴-acetylcytidine [1].

Links to other databases:

References:

1.	Ikeuchi, Y., Kitahara, K. and Suzuki, T. The RNA acetyltransferase driven by ATP hydrolysis synthesizes N⁴-acetylcytidine of tRNA anticodon. EMBO J. 27 (2008) 2194–2203. [DOI] [PMID: 18668122]
2.	Chimnaronk, S., Suzuki, T., Manita, T., Ikeuchi, Y., Yao, M., Suzuki, T. and Tanaka, I. RNA helicase module in an acetyltransferase that modifies a specific tRNA anticodon. EMBO J. 28 (2009) 1362–1373. [DOI] [PMID: 19322199]

[EC 2.3.1.193 created 2011]

2.3.1.194

Accepted name:

acetoacetyl-CoA synthase

Reaction:

acetyl-CoA + malonyl-CoA = acetoacetyl-CoA + CoA + CO₂

Other name(s):

NphT7

Systematic name:

acetyl-CoA:malonyl-CoA C-acetyltransferase (decarboxylating)

Comments:

The enzyme from the soil bacterium Streptomyces sp. CL190 produces acetoacetyl-CoA to be used for mevalonate production via the mevalonate pathway. Unlike the homologous EC 2.3.1.180 (β-ketoacyl-[acyl-carrier-protein] synthase III), this enzyme does not accept malonyl-[acyl-carrier-protein] as a substrate.

Links to other databases:

References:

1.	Okamura, E., Tomita, T., Sawa, R., Nishiyama, M. and Kuzuyama, T. Unprecedented acetoacetyl-coenzyme A synthesizing enzyme of the thiolase superfamily involved in the mevalonate pathway. Proc. Natl. Acad. Sci. USA 107 (2010) 11265–11270. [DOI] [PMID: 20534558]

[EC 2.3.1.194 created 2011]

2.3.1.195

Accepted name:

(Z)-3-hexen-1-ol acetyltransferase

Reaction:

acetyl-CoA + (3Z)-hex-3-en-1-ol = CoA + (3Z)-hex-3-en-1-yl acetate

Other name(s):

CHAT; At3g03480

Systematic name:

acetyl-CoA:(3Z)-hex-3-en-1-ol acetyltransferase

Comments:

The enzyme is resonsible for the production of (3Z)-hex-3-en-1-yl acetate, the major volatile compound released upon mechanical wounding of the leaves of Arabidopsis thaliana [1].

Links to other databases:

References:

1.	D'Auria, J.C., Pichersky, E., Schaub, A., Hansel, A. and Gershenzon, J. Characterization of a BAHD acyltransferase responsible for producing the green leaf volatile (Z)-3-hexen-1-yl acetate in Arabidopsis thaliana. Plant J. 49 (2007) 194–207. [DOI] [PMID: 17163881]
2.	D'Auria, J.C., Chen, F. and Pichersky, E. Characterization of an acyltransferase capable of synthesizing benzylbenzoate and other volatile esters in flowers and damaged leaves of Clarkia breweri. Plant Physiol. 130 (2002) 466–476. [DOI] [PMID: 12226525]

[EC 2.3.1.195 created 2011]

2.4.1.251

Accepted name:

GlcA-β-(1→2)-D-Man-α-(1→3)-D-Glc-β-(1→4)-D-Glc-α-1-diphospho-ditrans,octacis-undecaprenol 4-β-mannosyltransferase

Reaction:

GDP-mannose + GlcA-β-(1→2)-D-Man-α-(1→3)-D-Glc-β-(1→4)-D-Glc-α-1-diphospho-ditrans,octacis-undecaprenol = GDP + 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

For diagram of xanthan biosynthesis, click here

Other name(s):

GumI

Systematic name:

GDP-mannose:GlcA-β-(1→2)-D-Man-α-(1→3)-D-Glc-β-(1→4)-D-Glc-α-1-diphospho-ditrans,octacis-undecaprenol 4-β-mannosyltransferase

Comments:

The enzyme is involved in the biosynthesis of the exopolysaccharide xanthan.

Links to other databases:

References:

1.	Katzen, F., Ferreiro, D.U., Oddo, C.G., Ielmini, M.V., Becker, A., Puhler, A. and Ielpi, L. Xanthomonas campestris pv. campestris gum mutants: effects on xanthan biosynthesis and plant virulence. J. Bacteriol. 180 (1998) 1607–1617. [PMID: 9537354]
2.	Ielpi, L., Couso, R.O. and Dankert, M.A. Sequential assembly and polymerization of the polyprenol-linked pentasaccharide repeating unit of the xanthan polysaccharide in Xanthomonas campestris. J. Bacteriol. 175 (1993) 2490–2500. [DOI] [PMID: 7683019]
3.	Kim, S.Y., Kim, J.G., Lee, B.M. and Cho, J.Y. Mutational analysis of the gum gene cluster required for xanthan biosynthesis in Xanthomonas oryzae pv oryzae. Biotechnol. Lett. 31 (2009) 265–270. [DOI] [PMID: 18854951]

[EC 2.4.1.251 created 2011]

2.4.1.252

Accepted name:

GDP-mannose:cellobiosyl-diphosphopolyprenol α-mannosyltransferase

Reaction:

GDP-mannose + D-Glc-β-(1→4)-Glc-α-1-diphospho-ditrans,octacis-undecaprenol = GDP + D-Man-α-(1→3)-D-Glc-β-(1→4)-D-Glc-α-1-diphospho-ditrans,octacis-undecaprenol

For diagram of xanthan biosynthesis, click here

Other name(s):

GumH; AceA; α1,3-mannosyltransferase AceA

Systematic name:

GDP-mannose:D-Glc-β-(1→4)-Glc-α-1-diphospho-ditrans,octacis-undecaprenol 3-α-mannosyltransferase

Comments:

In the bacterium Gluconacetobacter xylinus (previously known as Acetobacter xylinum) the enzyme is involved in the biosynthesis of the exopolysaccharide acetan [1]. In Xanthomonas campestris the enzyme is involved in the biosynthesis of the exopolysaccharide xanthan [5].

Links to other databases:

References:

1.	Geremia, R.A., Roux, M., Ferreiro, D.U., Dauphin-Dubois, R., Lellouch, A.C. and Ielpi, L. Expression and biochemical characterisation of recombinant AceA, a bacterial α-mannosyltransferase. Mol. Gen. Genet. 261 (1999) 933–940. [PMID: 10485283]
2.	Abdian, P.L., Lellouch, A.C., Gautier, C., Ielpi, L. and Geremia, R.A. Identification of essential amino acids in the bacterial α-mannosyltransferase aceA. J. Biol. Chem. 275 (2000) 40568–40575. [DOI] [PMID: 11001941]
3.	Petroni, E.A. and Ielpi, L. Isolation and nucleotide sequence of the GDP-mannose:cellobiosyl-diphosphopolyprenol α-mannosyltransferase gene from Acetobacter xylinum. J. Bacteriol. 178 (1996) 4814–4821. [DOI] [PMID: 8759843]
4.	Lellouch, A.C., Watt, G.M., Geremia, R.A. and Flitsch, S.L. Phytanyl-pyrophosphate-linked substrate for a bacterial α-mannosyltransferase. Biochem. Biophys. Res. Commun. 272 (2000) 290–292. [DOI] [PMID: 10872841]
5.	Katzen, F., Ferreiro, D.U., Oddo, C.G., Ielmini, M.V., Becker, A., Puhler, A. and Ielpi, L. Xanthomonas campestris pv. campestris gum mutants: effects on xanthan biosynthesis and plant virulence. J. Bacteriol. 180 (1998) 1607–1617. [PMID: 9537354]

[EC 2.4.1.252 created 2011]

2.4.1.253

Accepted name:

baicalein 7-O-glucuronosyltransferase

Reaction:

UDP-D-glucuronate + baicalein = UDP + baicalin

Glossary:

baicalin = 5,6,7-trihydroxyflavone-7-O-β-D-glucuronate = 5,6-dihydroxy-4-oxo-2-phenyl-4H-chromen-7-yl β-D-glucupyranosiduronic acid
baicalein = 5,6,7-trihydroxyflavone = 5,6,7-trihydroxy-2-phenyl-4H-chromen-4-one
wogonin = 5,7-dihydroxy-8-methoxyflavone = 5,7-dihydroxy-8-methoxy-2-phenyl-4H-chromen-4-one
scutellarein = 4,5,6,7-tetrahydroxyflavone-7-O-β-D-glucoronate = 5,6,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one

Other name(s):

UBGAT

Systematic name:

UDP-D-glucuronate:5,6,7-trihydroxyflavone 7-O-glucuronosyltransferase

Comments:

The enzyme is specific for UDP-D-glucuronate as a sugar donor and flavones with substitution ortho- to the 7-OH group such as baicalein (6-OH), scutellarein (6-OH) and wogonin (8-OMe).

Links to other databases:

References:

1.	Nagashima, S., Hirotani, M. and Yoshikawa, T. Purification and characterization of UDP-glucuronate: baicalein 7-O-glucuronosyltransferase from Scutellaria baicalensis Georgi. cell suspension cultures. Phytochemistry 53 (2000) 533–538. [DOI] [PMID: 10724177]

[EC 2.4.1.253 created 2011]

2.4.1.254

Accepted name:

cyanidin-3-O-glucoside 2′′-O-glucuronosyltransferase

Reaction:

UDP-α-D-glucuronate + cyanidin 3-O-β-D-glucoside = UDP + cyanidin 3-O-(2-O-β-D-glucuronosyl)-β-D-glucoside

Glossary:

cyanidin = 3,3′,4′,5,7-pentahydroxyflavylium

Other name(s):

BpUGT94B1; UDP-glucuronic acid:anthocyanin glucuronosyltransferase; UDP-glucuronic acid:anthocyanidin 3-glucoside 2′-O-β-glucuronosyltransferase; BpUGAT; UDP-D-glucuronate:cyanidin-3-O-β-glucoside 2-O-β-glucuronosyltransferase

Systematic name:

UDP-α-D-glucuronate:cyanidin-3-O-β-D-glucoside 2-O-β-D-glucuronosyltransferase

Comments:

The enzyme is highly specific for cyanidin 3-O-glucosides and UDP-α-D-glucuronate. Involved in the production of glucuronosylated anthocyanins that are the origin of the red coloration of flowers of Bellis perennis [1].

Links to other databases:

References:

1.	Sawada, S., Suzuki, H., Ichimaida, F., Yamaguchi, M.A., Iwashita, T., Fukui, Y., Hemmi, H., Nishino, T. and Nakayama, T. UDP-glucuronic acid:anthocyanin glucuronosyltransferase from red daisy (Bellis perennis) flowers. Enzymology and phylogenetics of a novel glucuronosyltransferase involved in flower pigment biosynthesis. J. Biol. Chem. 280 (2005) 899–906. [DOI] [PMID: 15509561]
2.	Osmani, S.A., Bak, S., Imberty, A., Olsen, C.E. and Møller, B.L. Catalytic key amino acids and UDP-sugar donor specificity of a plant glucuronosyltransferase, UGT94B1: molecular modeling substantiated by site-specific mutagenesis and biochemical analyses. Plant Physiol. 148 (2008) 1295–1308. [DOI] [PMID: 18829982]

[EC 2.4.1.254 created 2011]

2.4.1.255

Accepted name:

protein O-GlcNAc transferase

Reaction:

(1) UDP-N-acetyl-α-D-glucosamine + [protein]-L-serine = UDP + [protein]-3-O-(N-acetyl-β-D-glucosaminyl)-L-serine
(2) UDP-N-acetyl-α-D-glucosamine + [protein]-L-threonine = UDP + [protein]-3-O-(N-acetyl-β-D-glucosaminyl)-L-threonine

Other name(s):

O-GlcNAc transferase; OGTase; O-linked N-acetylglucosaminyltransferase; uridine diphospho-N-acetylglucosamine:polypeptide β-N-acetylglucosaminyltransferase; protein O-linked β-N-acetylglucosamine transferase

Systematic name:

UDP-N-α-acetyl-D-glucosamine:[protein]-3-O-N-acetyl-β-D-glucosaminyl transferase

Comments:

Within higher eukaryotes post-translational modification of protein serines/threonines with N-acetylglucosamine (O-GlcNAc) is dynamic, inducible and abundant, regulating many cellular processes by interfering with protein phosphorylation. EC 2.4.1.255 (protein O-GlcNAc transferase) transfers GlcNAc onto substrate proteins and EC 3.2.1.169 (protein O-GlcNAcase) cleaves GlcNAc from the modified proteins.

Links to other databases:

References:

1.	Banerjee, S., Robbins, P.W. and Samuelson, J. Molecular characterization of nucleocytosolic O-GlcNAc transferases of Giardia lamblia and Cryptosporidium parvum. Glycobiology 19 (2009) 331–336. [DOI] [PMID: 18948359]
2.	Clarke, A.J., Hurtado-Guerrero, R., Pathak, S., Schuttelkopf, A.W., Borodkin, V., Shepherd, S.M., Ibrahim, A.F. and van Aalten, D.M. Structural insights into mechanism and specificity of O-GlcNAc transferase. EMBO J. 27 (2008) 2780–2788. [DOI] [PMID: 18818698]
3.	Rao, F.V., Dorfmueller, H.C., Villa, F., Allwood, M., Eggleston, I.M. and van Aalten, D.M. Structural insights into the mechanism and inhibition of eukaryotic O-GlcNAc hydrolysis. EMBO J. 25 (2006) 1569–1578. [DOI] [PMID: 16541109]
4.	Haltiwanger, R.S., Blomberg, M.A. and Hart, G.W. Glycosylation of nuclear and cytoplasmic proteins. Purification and characterization of a uridine diphospho-N-acetylglucosamine:polypeptide β-N-acetylglucosaminyltransferase. J. Biol. Chem. 267 (1992) 9005–9013. [PMID: 1533623]
5.	Lubas, W.A., Frank, D.W., Krause, M. and Hanover, J.A. O-Linked GlcNAc transferase is a conserved nucleocytoplasmic protein containing tetratricopeptide repeats. J. Biol. Chem. 272 (1997) 9316–9324. [DOI] [PMID: 9083068]
6.	Lazarus, M.B., Nam, Y., Jiang, J., Sliz, P. and Walker, S. Structure of human O-GlcNAc transferase and its complex with a peptide substrate. Nature 469 (2011) 564–567. [DOI] [PMID: 21240259]

[EC 2.4.1.255 created 2011]

2.5.1.93

Accepted name:

4-hydroxybenzoate geranyltransferase

Reaction:

geranyl diphosphate + 4-hydroxybenzoate = 3-geranyl-4-hydroxybenzoate + diphosphate

Other name(s):

PGT₁; PGT₂; 4HB geranyltransferase; 4HB:geranyltransferase; p-hydroxybenzoate geranyltransferase; PHB geranyltransferase; geranyl diphosphate:4-hydroxybenzoate geranyltransferase

Systematic name:

geranyl-diphosphate:4-hydroxybenzoate 3-geranyltransferase

Comments:

The enzyme is involved in shikonin biosynthesis. It has a strict substrate specificity for geranyl diphosphate and an absolute requirement for Mg²⁺ [2].

Links to other databases:

References:

1.	Ohara, K., Muroya, A., Fukushima, N. and Yazaki, K. Functional characterization of LePGT₁, a membrane-bound prenyltransferase involved in the geranylation of p-hydroxybenzoic acid. Biochem. J. 421 (2009) 231–241. [DOI] [PMID: 19392660]
2.	Muhlenweg, A., Melzer, M., Li, S.M. and Heide, L. 4-Hydroxybenzoate 3-geranyltransferase from Lithospermum erythrorhizon: purification of a plant membrane-bound prenyltransferase. Planta 205 (1998) 407–413. [DOI] [PMID: 9640665]
3.	Yazaki, K., Kunihisa, M., Fujisaki, T. and Sato, F. Geranyl diphosphate:4-hydroxybenzoate geranyltransferase from Lithospermum erythrorhizon. Cloning and characterization of a key enzyme in shikonin biosynthesis. J. Biol. Chem. 277 (2002) 6240–6246. [DOI] [PMID: 11744717]

[EC 2.5.1.93 created 2010]

2.5.1.94

Accepted name:

adenosyl-chloride synthase

Reaction:

S-adenosyl-L-methionine + chloride = 5-deoxy-5-chloroadenosine + L-methionine

Glossary:

5-deoxy-5-chloroadenosine = 5′-chloro-5′-deoxyadenosine

Other name(s):

chlorinase; 5′-chloro-5′-deoxyadenosine synthase

Systematic name:

S-adenosyl-L-methionine:chloride adenosyltransferase

Comments:

This enzyme, isolated from the marine bacterium Salinispora tropica, catalyses an early step in the pathway leading to biosynthesis of the proteosome inhibitor salinosporamide A. The enzyme is very similar to EC 2.5.1.63, adenosyl-fluoride synthase, but does not accept fluoride.

Links to other databases:

References:

1.	Eustaquio, A.S., Pojer, F., Noel, J.P. and Moore, B.S. Discovery and characterization of a marine bacterial SAM-dependent chlorinase. Nat. Chem. Biol. 4 (2008) 69–74. [DOI] [PMID: 18059261]

[EC 2.5.1.94 created 2011]

2.7.1.169

Accepted name:

pantoate kinase

Reaction:

ATP + (R)-pantoate = ADP + (R)-4-phosphopantoate

Other name(s):

PoK; TK2141 protein

Systematic name:

ATP:(R)-pantoate 4-phosphotransferase

Comments:

The conversion of (R)-pantoate to (R)-4′-phosphopantothenate is part of the pathway leading to biosynthesis of 4′-phosphopantetheine, an essential cofactor of coenzyme A and acyl-carrier protein. In bacteria and eukaryotes this conversion is performed by condensation with β-alanine, followed by phosphorylation (EC 6.3.2.1 and EC 2.7.1.33, respectively). In archaea the order of these two steps is reversed, and phosphorylation precedes condensation with β-alanine.

Links to other databases:

References:

1.	Yokooji, Y., Tomita, H., Atomi, H. and Imanaka, T. Pantoate kinase and phosphopantothenate synthetase, two novel enzymes necessary for CoA biosynthesis in the Archaea. J. Biol. Chem. 284 (2009) 28137–28145. [DOI] [PMID: 19666462]

[EC 2.7.1.169 created 2011]

*EC

2.7.4.14

Accepted name:

UMP/CMP kinase

Reaction:

(1) ATP + (d)CMP = ADP + (d)CDP
(2) ATP + UMP = ADP + UDP

Other name(s):

cytidylate kinase (misleading); deoxycytidylate kinase (misleading); CTP:CMP phosphotransferase (misleading); dCMP kinase (misleading); deoxycytidine monophosphokinase (misleading); UMP-CMP kinase; ATP:UMP-CMP phosphotransferase; pyrimidine nucleoside monophosphate kinase; uridine monophosphate-cytidine monophosphate phosphotransferase

Systematic name:

ATP:(d)CMP/UMP phosphotransferase

Comments:

This eukaryotic enzyme is a bifunctional enzyme that catalyses the phosphorylation of both CMP and UMP with similar efficiency. dCMP can also act as acceptor. Different from the monofunctional prokaryotic enzymes EC 2.7.4.25, (d)CMP kinase and EC 2.7.4.22, UMP kinase.

Links to other databases:

BRENDA, EXPASY, Gene, GTD, KEGG, PDB, CAS registry number: 37278-21-0

References:

1.	Hurwitz, J. The enzymatic incorporation of ribonucleotides into polydeoxynucleotide material. J. Biol. Chem. 234 (1959) 2351–2358. [PMID: 14405566]
2.	Ruffner, B.W., Jr. and Anderson, E.P. Adenosine triphosphate: uridine monophosphate-cytidine monophosphate phosphotransferase from Tetrahymena pyriformis. J. Biol. Chem. 244 (1969) 5994–6002. [PMID: 5350952]
3.	Scheffzek, K., Kliche, W., Wiesmuller, L. and Reinstein, J. Crystal structure of the complex of UMP/CMP kinase from Dictyostelium discoideum and the bisubstrate inhibitor P1-(5′-adenosyl) P5-(5′-uridyl) pentaphosphate (UP5A) and Mg²⁺ at 2.2 Å: implications for water-mediated specificity. Biochemistry 35 (1996) 9716–9727. [DOI] [PMID: 8703943]
4.	Zhou, L., Lacroute, F. and Thornburg, R. Cloning, expression in Escherichia coli, and characterization of Arabidopsis thaliana UMP/CMP kinase. Plant Physiol. 117 (1998) 245–254. [PMID: 9576794]
5.	Van Rompay, A.R., Johansson, M. and Karlsson, A. Phosphorylation of deoxycytidine analog monophosphates by UMP-CMP kinase: molecular characterization of the human enzyme. Mol. Pharmacol. 56 (1999) 562–569. [PMID: 10462544]

[EC 2.7.4.14 created 1961 as EC 2.7.4.5, transferred 1972 to EC 2.7.4.14, modified 1980, modified 2011]

2.7.4.25

Accepted name:

(d)CMP kinase

Reaction:

ATP + (d)CMP = ADP + (d)CDP

Glossary:

CMP = cytidine monophosphate
dCMP = deoxycytidine monophosphate
CDP = cytidine diphosphate
dCDP = deoxycytidine diphosphate
UMP = uridine monophosphate
UDP = uridine diphosphate

Other name(s):

cmk (gene name); prokaryotic cytidylate kinase; deoxycytidylate kinase (misleading); dCMP kinase (misleading); deoxycytidine monophosphokinase (misleading)

Systematic name:

ATP:(d)CMP phosphotransferase

Comments:

The prokaryotic cytidine monophosphate kinase specifically phosphorylates CMP (or dCMP), using ATP as the preferred phosphoryl donor. Unlike EC 2.7.4.14, a eukaryotic enzyme that phosphorylates UMP and CMP with similar efficiency, the prokaryotic enzyme phosphorylates UMP with very low rates, and this function is catalysed in prokaryotes by EC 2.7.4.22, UMP kinase. The enzyme phosphorylates dCMP nearly as well as it does CMP [1].

Links to other databases:

References:

1.	Bertrand, T., Briozzo, P., Assairi, L., Ofiteru, A., Bucurenci, N., Munier-Lehmann, H., Golinelli-Pimpaneau, B., Barzu, O. and Gilles, A.M. Sugar specificity of bacterial CMP kinases as revealed by crystal structures and mutagenesis of Escherichia coli enzyme. J. Mol. Biol. 315 (2002) 1099–1110. [DOI] [PMID: 11827479]
2.	Thum, C., Schneider, C.Z., Palma, M.S., Santos, D.S. and Basso, L.A. The Rv1712 Locus from Mycobacterium tuberculosis H37Rv codes for a functional CMP kinase that preferentially phosphorylates dCMP. J. Bacteriol. 191 (2009) 2884–2887. [DOI] [PMID: 19181797]

[EC 2.7.4.25 created 2011]

2.7.7.21

Transferred entry:

tRNA cytidylyltransferase. Now EC 2.7.7.72, CCA tRNA nucleotidyltransferase

[EC 2.7.7.21 created 1965, deleted 2010]

2.7.7.25

Transferred entry:

tRNA adenylyltransferase. Now EC 2.7.7.72, CCA tRNA nucleotidyltransferase

[EC 2.7.7.25 created 1965, deleted 2010]

2.7.7.72

Accepted name:

CCA tRNA nucleotidyltransferase

Reaction:

a tRNA precursor + 2 CTP + ATP = a tRNA with a 3′ CCA end + 3 diphosphate (overall reaction)
(1a) a tRNA precursor + CTP = a tRNA with a 3′ cytidine end + diphosphate
(1b) a tRNA with a 3′ cytidine + CTP = a tRNA with a 3′ CC end + diphosphate
(1c) a tRNA with a 3′ CC end + ATP = a tRNA with a 3′ CCA end + diphosphate

Other name(s):

CCA-adding enzyme; tRNA adenylyltransferase; tRNA cytidylyltransferase; tRNA CCA-pyrophosphorylase; tRNA-nucleotidyltransferase; transfer-RNA nucleotidyltransferase; transfer ribonucleic acid nucleotidyl transferase; CTP(ATP):tRNA nucleotidyltransferase; transfer ribonucleate adenylyltransferase; transfer ribonucleate adenyltransferase; transfer RNA adenylyltransferase; transfer ribonucleate nucleotidyltransferase; ATP (CTP):tRNA nucleotidyltransferase; ribonucleic cytidylic cytidylic adenylic pyrophosphorylase; transfer ribonucleic adenylyl (cytidylyl) transferase; transfer ribonucleic-terminal trinucleotide nucleotidyltransferase; transfer ribonucleate cytidylyltransferase; ribonucleic cytidylyltransferase; -C-C-A pyrophosphorylase; ATP(CTP)-tRNA nucleotidyltransferase; tRNA adenylyl(cytidylyl)transferase; CTP:tRNA cytidylyltransferase

Systematic name:

CTP,CTP,ATP:tRNA cytidylyl,cytidylyl,adenylyltransferase

Comments:

The acylation of all tRNAs with an amino acid occurs at the terminal ribose of a 3′ CCA sequence. The CCA sequence is added to the tRNA precursor by stepwise nucleotide addition performed by a single enzyme that is ubiquitous in all living organisms. Although the enzyme has the option of releasing the product after each addition, it prefers to stay bound to the product and proceed with the next addition [5].

Links to other databases:

References:

1.	Schofield, P. and Williams, K.R. Purification and some properties of Escherichia coli tRNA nucleotidyltransferase. J. Biol. Chem. 252 (1977) 5584–5588. [PMID: 328503]
2.	Shi, P.Y., Maizels, N. and Weiner, A.M. CCA addition by tRNA nucleotidyltransferase: polymerization without translocation. EMBO J. 17 (1998) 3197–3206. [DOI] [PMID: 9606201]
3.	Augustin, M.A., Reichert, A.S., Betat, H., Huber, R., Morl, M. and Steegborn, C. Crystal structure of the human CCA-adding enzyme: insights into template-independent polymerization. J. Mol. Biol. 328 (2003) 985–994. [DOI] [PMID: 12729736]
4.	Yakunin, A.F., Proudfoot, M., Kuznetsova, E., Savchenko, A., Brown, G., Arrowsmith, C.H. and Edwards, A.M. The HD domain of the Escherichia coli tRNA nucleotidyltransferase has 2′,3′-cyclic phosphodiesterase, 2′-nucleotidase, and phosphatase activities. J. Biol. Chem. 279 (2004) 36819–36827. [DOI] [PMID: 15210699]
5.	Hou, Y.M. CCA addition to tRNA: implications for tRNA quality control. IUBMB Life 62 (2010) 251–260. [DOI] [PMID: 20101632]

[EC 2.7.7.72 created 1965 as EC 2.7.7.21 and EC 2.7.7.25, both transferred 2010 to EC 2.7.7.72]

2.7.7.73

Accepted name:

sulfur carrier protein ThiS adenylyltransferase

Reaction:

ATP + [ThiS] = diphosphate + adenylyl-[ThiS]

Other name(s):

thiF (gene name)

Systematic name:

ATP:[ThiS] adenylyltransferase

Comments:

Binds Zn²⁺. The enzyme catalyses the adenylation of ThiS, a sulfur carrier protein involved in the biosynthesis of thiamine. The enzyme shows significant structural similarity to ubiquitin-activating enzyme [3,4]. In Escherichia coli, but not in Bacillus subtilis, the enzyme forms a cross link from Cys-184 to the ThiS carboxy terminus (the position that is also thiolated) via an acyldisulfide [2].

Links to other databases:

References:

1.	Taylor, S.V., Kelleher, N.L., Kinsland, C., Chiu, H.J., Costello, C.A., Backstrom, A.D., McLafferty, F.W. and Begley, T.P. Thiamin biosynthesis in Escherichia coli. Identification of this thiocarboxylate as the immediate sulfur donor in the thiazole formation. J. Biol. Chem. 273 (1998) 16555–16560. [DOI] [PMID: 9632726]
2.	Xi, J., Ge, Y., Kinsland, C., McLafferty, F.W. and Begley, T.P. Biosynthesis of the thiazole moiety of thiamin in Escherichia coli: identification of an acyldisulfide-linked protein^--protein conjugate that is functionally analogous to the ubiquitin/E1 complex. Proc. Natl. Acad. Sci. USA 98 (2001) 8513–8518. [DOI] [PMID: 11438688]
3.	Duda, D.M., Walden, H., Sfondouris, J. and Schulman, B.A. Structural analysis of Escherichia coli ThiF. J. Mol. Biol. 349 (2005) 774–786. [DOI] [PMID: 15896804]
4.	Lehmann, C., Begley, T.P. and Ealick, S.E. Structure of the Escherichia coli ThiS-ThiF complex, a key component of the sulfur transfer system in thiamin biosynthesis. Biochemistry 45 (2006) 11–19. [DOI] [PMID: 16388576]

[EC 2.7.7.73 created 2011]

2.7.8.31

Accepted name:

undecaprenyl-phosphate glucose phosphotransferase

Reaction:

UDP-glucose + ditrans,octacis-undecaprenyl phosphate = UMP + α-D-glucopyranosyl-diphospho-ditrans,octacis-undecaprenol

For diagram of xanthan biosynthesis, click here

Other name(s):

GumD; undecaprenylphosphate glucosylphosphate transferase

Systematic name:

UDP-glucose:ditrans,octacis-undecaprenyl-phosphate glucose phosphotransferase

Comments:

The enzyme is involved in biosynthesis of xanthan.

Links to other databases:

References:

1.	Ielpi, L., Couso, R.O. and Dankert, M.A. Sequential assembly and polymerization of the polyprenol-linked pentasaccharide repeating unit of the xanthan polysaccharide in Xanthomonas campestris. J. Bacteriol. 175 (1993) 2490–2500. [DOI] [PMID: 7683019]
2.	Katzen, F., Ferreiro, D.U., Oddo, C.G., Ielmini, M.V., Becker, A., Puhler, A. and Ielpi, L. Xanthomonas campestris pv. campestris gum mutants: effects on xanthan biosynthesis and plant virulence. J. Bacteriol. 180 (1998) 1607–1617. [PMID: 9537354]
3.	Kim, S.Y., Kim, J.G., Lee, B.M. and Cho, J.Y. Mutational analysis of the gum gene cluster required for xanthan biosynthesis in Xanthomonas oryzae pv oryzae. Biotechnol. Lett. 31 (2009) 265–270. [DOI] [PMID: 18854951]

[EC 2.7.8.31 created 2011]

2.7.8.32

Accepted name:

3-O-α-D-mannopyranosyl-α-D-mannopyranose xylosylphosphotransferase

Reaction:

UDP-xylose + 3-O-α-D-mannopyranosyl-α-D-mannopyranose = UMP + 3-O-(6-O-α-D-xylosylphospho-α-D-mannopyranosyl)-α-D-mannopyranose

Glossary:

O-α-D-xylosylphospho-α-D-mannopyranosyl)-α-D-mannopyranose = O-α-D-xylosylphosphono-α-D-mannopyranosyl)-α-D-mannopyranose

Other name(s):

XPT1

Systematic name:

UDP-D-xylose:3-O-α-D-mannopyranosyl-α-D-mannopyranose xylosylphosphotransferase

Comments:

Mn²⁺ required for activity. The enzyme is specific for mannose as an acceptor but is flexible as to the structural context of the mannosyl disaccharide.

Links to other databases:

References:

1.	Reilly, M.C., Levery, S.B., Castle, S.A., Klutts, J.S. and Doering, T.L. A novel xylosylphosphotransferase activity discovered in Cryptococcus neoformans. J. Biol. Chem. 284 (2009) 36118–36127. [DOI] [PMID: 19864415]

[EC 2.7.8.32 created 2011]

*EC

2.8.2.33

Accepted name:

N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase

Reaction:

(1) 3′-phospho-5′-adenylyl sulfate + [dermatan]-4-O-sulfo-N-acetyl-D-galactosamine = adenosine 3′,5′-bisphosphate + [dermatan]-4,6-di-O-sulfo-N-acetyl-D-galactosamine
(2) 3′-phospho-5′-adenylyl sulfate + [chondroitin]-4-O-sulfo-N-acetyl-D-galactosamine = adenosine 3′,5′-bisphosphate + [chondroitin]-4,6-di-O-sulfo-N-acetyl-D-galactosamine

Other name(s):

GalNAc4S-6ST; CHST15 (gene name); 3′-phosphoadenylyl-sulfate:[dermatan]-4-O-sulfo-N-acetyl-D-galactosamine 6-O-sulfotransferase

Systematic name:

3′-phosphoadenylyl-sulfate:[dermatan]-4-O-sulfo-N-acetyl-D-galactosamine 6-O-sulfonotransferase

Comments:

The enzyme is activated by divalent cations and reduced glutathione. The enzyme from human transfers sulfate to position 6 of both internal residues and non-reducing terminal GalNAc 4-sulfate residues of chondroitin sulfate and dermatan sulfate. Oligosaccharides derived from chondroitin sulfate also serve as acceptors but chondroitin sulfate E, keratan sulfate and heparan sulfate do not. Differs from EC 2.8.2.17, chondroitin 6-sulfotransferase, in being able to use both chondroitin and dermatan as effective substrates

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 242469-38-1

References:

1.	Ito, Y. and Habuchi, O. Purification and characterization of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase from the squid cartilage. J. Biol. Chem. 275 (2000) 34728–34736. [DOI] [PMID: 10871629]
2.	Ohtake, S., Ito, Y., Fukuta, M. and Habuchi, O. Human N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase cDNA is related to human B cell recombination activating gene-associated gene. J. Biol. Chem. 276 (2001) 43894–43900. [DOI] [PMID: 11572857]

[EC 2.8.2.33 created 2005, modified 2010]

2.8.2.35

Accepted name:

dermatan 4-sulfotransferase

Reaction:

3′-phospho-5′-adenylyl sulfate + [dermatan]-N-acetyl-D-galactosamine = adenosine 3′,5′-bisphosphate + [dermatan]-4-O-sulfo-N-acetyl-D-galactosamine

Other name(s):

dermatan-specific N-acetylgalactosamine 4-O-sulfotransferase; dermatan-4-sulfotransferase-1; dermatan-4-sulfotransferase 1; D4ST-1; dermatan N-acetylgalactosamine 4-O-sulfotransferase; CHST14 protein; CHST14; 3′-phospho-5′-adenylyl sulfate:[dermatan]-N-acetyl-D-galactosamine 4-sulfotransferase

Systematic name:

3′-phospho-5′-adenylyl sulfate:[dermatan]-N-acetyl-D-galactosamine 4-sulfonotransferase

Comments:

The sulfation takes place at the 4-position of N-acetyl-D-galactosamine residues of dermatan. D4ST-1 shows a strong preference in vitro for sulfate transfer to IdoUAα(1,3)GalNAcβ(1,4) that is flanked by GlcUAβ(1,3)GalNAcβ(1,4) as compared with IdoUAα(1,3)GalNAcβ(1,4) flanked by IdoUAα(1,3)GalNAcβ(1,4) [1].

Links to other databases:

References:

1.	Evers, M.R., Xia, G., Kang, H.G., Schachner, M. and Baenziger, J.U. Molecular cloning and characterization of a dermatan-specific N-acetylgalactosamine 4-O-sulfotransferase. J. Biol. Chem. 276 (2001) 36344–36353. [DOI] [PMID: 11470797]
2.	Mikami, T., Mizumoto, S., Kago, N., Kitagawa, H. and Sugahara, K. Specificities of three distinct human chondroitin/dermatan N-acetylgalactosamine 4-O-sulfotransferases demonstrated using partially desulfated dermatan sulfate as an acceptor: implication of differential roles in dermatan sulfate biosynthesis. J. Biol. Chem. 278 (2003) 36115–36127. [DOI] [PMID: 12847091]
3.	Pacheco, B., Maccarana, M. and Malmstrom, A. Dermatan 4-O-sulfotransferase 1 is pivotal in the formation of iduronic acid blocks in dermatan sulfate. Glycobiology 19 (2009) 1197–1203. [DOI] [PMID: 19661164]
4.	Mitsunaga, C., Mikami, T., Mizumoto, S., Fukuda, J. and Sugahara, K. Chondroitin sulfate/dermatan sulfate hybrid chains in the development of cerebellum. Spatiotemporal regulation of the expression of critical disulfated disaccharides by specific sulfotransferases. J. Biol. Chem. 281 (2006) 18942–18952. [DOI] [PMID: 16702220]

[EC 2.8.2.35 created 2010]

3.1.2.28

Accepted name:

1,4-dihydroxy-2-naphthoyl-CoA hydrolase

Reaction:

1,4-dihydroxy-2-naphthoyl-CoA + H₂O = 1,4-dihydroxy-2-naphthoate + CoA

For diagram of vitamin K biosynthesis, click here

Other name(s):

menI (gene name); ydiL (gene name)

Systematic name:

1,4-dihydroxy-2-naphthoyl-CoA hydrolase

Comments:

This enzyme participates in the synthesis of menaquinones [4], phylloquinone [3], as well as several plant pigments [1,2]. The enzyme from the cyanobacterium Synechocystis sp. PCC 6803 does not accept benzoyl-CoA or phenylacetyl-CoA as substrates [3].

Links to other databases:

References:

1.	Muller, W. and Leistner, E. 1,4-Naphthoquinone, an intermediate in juglone (5-hydroxy-1,4-naphthoquinone) biosynthesis. Phytochemistry 15 (1976) 407–410.
2.	Eichinger, D., Bacher, A., Zenk, M.H. and Eisenreich, W. Quantitative assessment of metabolic flux by ¹³C NMR analysis. Biosynthesis of anthraquinones in Rubia tinctorum. J. Am. Chem. Soc. 121 (1999) 7469–7475.
3.	Widhalm, J.R., van Oostende, C., Furt, F. and Basset, G.J. A dedicated thioesterase of the Hotdog-fold family is required for the biosynthesis of the naphthoquinone ring of vitamin K₁. Proc. Natl. Acad. Sci. USA 106 (2009) 5599–5603. [DOI] [PMID: 19321747]
4.	Chen, M., Ma, X., Chen, X., Jiang, M., Song, H. and Guo, Z. Identification of a hotdog fold thioesterase involved in the biosynthesis of menaquinone in Escherichia coli. J. Bacteriol. 195 (2013) 2768–2775. [DOI] [PMID: 23564174]

[EC 3.1.2.28 created 2010]

3.1.7.7

Transferred entry:

(–)-drimenol synthase. Now EC 4.2.3.194, (–)-drimenol synthase

[EC 3.1.7.7 created 2011, deleted 2017]

3.2.1.166

Accepted name:

heparanase

Reaction:

endohydrolysis of (1→4)-β-D-glycosidic bonds of heparan sulfate chains in heparan sulfate proteoglycan

Other name(s):

Hpa1 heparanase; Hpa1; heparanase 1; heparanase-1; C1A heparanase; HPSE

Systematic name:

heparan sulfate N-sulfo-D-glucosamine endoglucanase

Comments:

Heparanase cleaves the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo group [2]. Heparanase-1 cuts macromolecular heparin into fragments of 5000–20000 Da [5]. The enzyme cleaves the heparan sulfate glycosaminoglycans from proteoglycan core proteins and degrades them to small oligosaccharides. Inside cells, the enzyme is important for the normal catabolism of heparan sulfate proteoglycans, generating glycosaminoglycan fragments that are then transported to lysosomes and completely degraded. When secreted, heparanase degrades basement membrane heparan sulfate glycosaminoglycans at sites of injury or inflammation, allowing extravasion of immune cells into nonvascular spaces and releasing factors that regulate cell proliferation and angiogenesis [1].

Links to other databases:

References:

1.	Bame, K.J. Heparanases: endoglycosidases that degrade heparan sulfate proteoglycans. Glycobiology 11 (2001) 91R–98R. [DOI] [PMID: 11445547]
2.	Peterson, S.B. and Liu, J. Unraveling the specificity of heparanase utilizing synthetic substrates. J. Biol. Chem. 285 (2010) 14504–14513. [DOI] [PMID: 20181948]
3.	Pikas, D.S., Li, J.P., Vlodavsky, I. and Lindahl, U. Substrate specificity of heparanases from human hepatoma and platelets. J. Biol. Chem. 273 (1998) 18770–18777. [DOI] [PMID: 9668050]
4.	Okada, Y., Yamada, S., Toyoshima, M., Dong, J., Nakajima, M. and Sugahara, K. Structural recognition by recombinant human heparanase that plays critical roles in tumor metastasis. Hierarchical sulfate groups with different effects and the essential target disulfated trisaccharide sequence. J. Biol. Chem. 277 (2002) 42488–42495. [DOI] [PMID: 12213822]
5.	Vreys, V. and David, G. Mammalian heparanase: what is the message. J. Cell. Mol. Med. 11 (2007) 427–452. [DOI] [PMID: 17635638]
6.	Gong, F., Jemth, P., Escobar Galvis, M.L., Vlodavsky, I., Horner, A., Lindahl, U. and Li, J.P. Processing of macromolecular heparin by heparanase. J. Biol. Chem. 278 (2003) 35152–35158. [DOI] [PMID: 12837765]
7.	Toyoshima, M. and Nakajima, M. Human heparanase. Purification, characterization, cloning, and expression. J. Biol. Chem. 274 (1999) 24153–24160. [DOI] [PMID: 10446189]
8.	Miao, H.Q., Navarro, E., Patel, S., Sargent, D., Koo, H., Wan, H., Plata, A., Zhou, Q., Ludwig, D., Bohlen, P. and Kussie, P. Cloning, expression, and purification of mouse heparanase. Protein Expr. Purif. 26 (2002) 425–431. [DOI] [PMID: 12460766]
9.	Hammond, E., Li, C.P. and Ferro, V. Development of a colorimetric assay for heparanase activity suitable for kinetic analysis and inhibitor screening. Anal. Biochem. 396 (2010) 112–116. [DOI] [PMID: 19748475]

[EC 3.2.1.166 created 2010]

3.2.1.167

Accepted name:

baicalin-β-D-glucuronidase

Reaction:

baicalin + H₂O = baicalein + D-glucuronate

Glossary:

baicalin = 5,6,7-trihydroxyflavone-7-O-β-D-glucuronate = 5,6-dihydroxy-4-oxo-2-phenyl-4H-chromen-7-yl β-D-glucupyranosiduronic acid
baicalein = 5,6,7-trihydroxyflavone = 5,6,7-trihydroxy-2-phenyl-4H-chromen-4-one
wogonin = 5,7-dihydroxy-8-methoxyflavone = 5,7-dihydroxy-8-methoxy-2-phenyl-4H-chromen-4-one
oroxylin = 5,7-dihydroxy-6-methoxyflavone = 5,7-dihydroxy-6-methoxy-2-phenyl-4H-1-benzopyran-4-one

Other name(s):

baicalinase

Systematic name:

5,6,7-trihydroxyflavone-7-O-β-D-glucupyranosiduronate glucuronosylhydrolase

Comments:

The enzyme also hydrolyses wogonin 7-O-β-D-glucuronide and oroxylin 7-O-β-D-glucuronide with lower efficiency [4]. Neglegible activity with p-nitrophenyl-β-D-glucuronide [2].

Links to other databases:

References:

1.	Ikegami, F., Matsunae, K., Hisamitsu, M., Kurihara, T., Yamamoto, T. and Murakoshi, I. Purification and properties of a plant β-D-glucuronidase form Scutellaria root. Biol. Pharm. Bull. 18 (1995) 1531–1534. [PMID: 8593473]
2.	Zhang, C., Zhang, Y., Chen, J. and Liang, X. Purification and characterization of baicalin-β-D-glucuronidase hydrolyzing baicalin to baicalein from fresh roots of Scutellaria viscidula Bge. Proc. Biochem. 40 (2005) 1911–1915.
3.	Sasaki, K., Taura, F., Shoyama, Y. and Morimoto, S. Molecular characterization of a novel β-glucuronidase from Scutellaria baicalensis Georgi. J. Biol. Chem. 275 (2000) 27466–27472. [DOI] [PMID: 10858442]
4.	Morimoto, S., Harioka, T. and Shoyama, Y. Purification and characterization of flavone-specific β-glucuronidase from callus cultures of Scutellaria baicalensis Georgi. Planta 195 (1995) 535–540.

[EC 3.2.1.167 created 2011]

3.2.1.168

Accepted name:

hesperidin 6-O-α-L-rhamnosyl-β-D-glucosidase

Reaction:

hesperidin + H₂O = hesperetin + rutinose

Glossary:

hesperetin = 5,7,3′-trihydroxy-4′-methoxyflavanone
hesperidin = hesperetin 7-(6-O-α-L-rhamnopyranosyl-β-D-glucopyranoside)
rutinose = 6-O-α-L-rhamnopyranosyl-D-glucose

Other name(s):

AnRut; rutinosidase

Systematic name:

hesperetin 7-(6-O-α-L-rhamnopyranosyl-β-D-glucopyranoside) 6-O-α-rhamnopyranosyl-β-glucohydrolase

Comments:

The enzyme exhibits high specificity towards 7-O-linked flavonoid β-rutinosides.

Links to other databases:

References:

1.	Mazzaferro, L., Piñuel, L., Minig, M. and Breccia, J.D. Extracellular monoenzyme deglycosylation system of 7-O-linked flavonoid β-rutinosides and its disaccharide transglycosylation activity from Stilbella fimetaria. Arch. Microbiol. 192 (2010) 383–393. [DOI] [PMID: 20358178]
2.	Mazzaferro, L., Piñuel, L., Minig, M. and Breccia, J.D. Erratum to: Extracellular monoenzyme deglycosylation system of 7-O-linked flavonoid β-rutinosides and its disaccharide transglycosylation activity from Stilbella fimetaria. Arch. Microbiol. 193 (2011) 461.

[EC 3.2.1.168 created 2011]

3.2.1.169

Accepted name:

protein O-GlcNAcase

Reaction:

(1) [protein]-3-O-(N-acetyl-β-D-glucosaminyl)-L-serine + H₂O = [protein]-L-serine + N-acetyl-D-glucosamine
(2) [protein]-3-O-(N-acetyl-β-D-glucosaminyl)-L-theronine + H₂O = [protein]-L-threonine + N-acetyl-D-glucosamine

Other name(s):

OGA; glycoside hydrolase O-GlcNAcase; O-GlcNAcase; BtGH84; O-GlcNAc hydrolase

Systematic name:

[protein]-3-O-(N-acetyl-β-D-glucosaminyl)-L-serine/threonine N-acetylglucosaminyl hydrolase

Comments:

Links to other databases:

References:

1.	Gao, Y., Wells, L., Comer, F.I., Parker, G.J. and Hart, G.W. Dynamic O-glycosylation of nuclear and cytosolic proteins: cloning and characterization of a neutral, cytosolic β-N-acetylglucosaminidase from human brain. J. Biol. Chem. 276 (2001) 9838–9845. [DOI] [PMID: 11148210]
2.	Wells, L., Gao, Y., Mahoney, J.A., Vosseller, K., Chen, C., Rosen, A. and Hart, G.W. Dynamic O-glycosylation of nuclear and cytosolic proteins: further characterization of the nucleocytoplasmic β-N-acetylglucosaminidase, O-GlcNAcase. J. Biol. Chem. 277 (2002) 1755–1761. [PMID: 11788610]
3.	Cetinbas, N., Macauley, M.S., Stubbs, K.A., Drapala, R. and Vocadlo, D.J. Identification of Asp¹⁷⁴ and Asp¹⁷⁵ as the key catalytic residues of human O-GlcNAcase by functional analysis of site-directed mutants. Biochemistry 45 (2006) 3835–3844. [DOI] [PMID: 16533067]
4.	Dennis, R.J., Taylor, E.J., Macauley, M.S., Stubbs, K.A., Turkenburg, J.P., Hart, S.J., Black, G.N., Vocadlo, D.J. and Davies, G.J. Structure and mechanism of a bacterial β-glucosaminidase having O-GlcNAcase activity. Nat. Struct. Mol. Biol. 13 (2006) 365–371. [DOI] [PMID: 16565725]
5.	Kim, E.J., Kang, D.O., Love, D.C. and Hanover, J.A. Enzymatic characterization of O-GlcNAcase isoforms using a fluorogenic GlcNAc substrate. Carbohydr. Res. 341 (2006) 971–982. [DOI] [PMID: 16584714]
6.	Dong, D.L. and Hart, G.W. Purification and characterization of an O-GlcNAc selective N-acetyl-β-D-glucosaminidase from rat spleen cytosol. J. Biol. Chem. 269 (1994) 19321–19330. [PMID: 8034696]

[EC 3.2.1.169 created 2011]

*EC

3.4.21.6

Accepted name:

coagulation factor Xa

Reaction:

Selective cleavage of Arg┼Thr and then Arg┼Ile bonds in prothrombin to form thrombin

Other name(s):

thrombokinase; prothrombase; prothrombinase; activated blood-coagulation factor X; autoprothrombin C; thromboplastin; plasma thromboplastin; factor Xa; activated Stuart-Prower factor; activated factor X

Comments:

A blood coagulation factor formed from the proenzyme factor X by limited proteolysis. Factor X is a glycoprotein composed of a heavy chain and a light chain, which are generated from a precursor protein by the excision of the tripeptide RKR and held together by one or more disulfide bonds. The activated factor Xa converts prothrombin to thrombin in the presence of factor Va, Ca²⁺ and phospholipids. Scutelarin (EC 3.4.21.60) has similar specificity, but does not require factor Va.

Links to other databases:

BRENDA, Gene, KEGG, MEROPS, PDB, CAS registry number: 9002-05-5

References:

1.	Fujikawa, K. and Davie, E.W. Bovine factor X (Stuart factor). Methods Enzymol. 45 (1976) 89–95. [DOI] [PMID: 1012041]
2.	Jesty, J. and Nemerson, Y. The activation of bovine coagulation factor X. Methods Enzymol. 45 (1976) 95–107. [DOI] [PMID: 1012042]
3.	Davie, E.W., Fujikawa, K., Kurachi, K. and Kisiel, W. The role of serine proteases in the blood coagulation cascade. Adv. Enzymol. 48 (1979) 277–318. [PMID: 367103]
4.	Jackson, C.M. and Nemerson, Y. Blood coagulation. Annu. Rev. Biochem. 49 (1980) 765–811. [DOI] [PMID: 6996572]
5.	McMullen, B.A., Fujikawa, K., Kisiel, W., Sasagawa, T., Howald, W.N., Kwa, E.Y. and Weinstein, B. Complete amino acid sequence of the light chain of human blood coagulation factor X: evidence for identification of residue 63 as β-hydroxyaspartic acid. Biochemistry 22 (1983) 2875–2884. [PMID: 6871167]
6.	Cho, K., Tanaka, T., Cook, R.R., Kisiel, W., Fujikawa, K., Kurachi, K. and Powers, J.C. Active-site mapping of bovine and human blood coagulation serine proteases using synthetic peptide 4-nitroanilide and thio ester substrates. Biochemistry 23 (1984) 644–650. [PMID: 6370301]

[EC 3.4.21.6 created 1972, modified 2011]

*EC

3.4.21.60

Accepted name:

scutelarin

Reaction:

Selective cleavage of Arg┼Thr and Arg┼Ile in prothrombin to form thrombin and two inactive fragments

Other name(s):

taipan activator; Oxyuranus scutellatus prothrombin-activating proteinase

Comments:

From the venom of the Taipan snake (Oxyuranus scutellatus). Converts prothrombin to thrombin. Specificity is similar to that of Factor Xa (EC 3.4.21.6). However, unlike Factor Xa this enzyme can cleave its target in the absence of coagulation Factor Va. Activity is potentiated by phospholipid and Ca²⁺ which binds via γ-carboxyglutamic acid residues. Similar enzymes are known from the venom of other Australian elapid snakes, including Pseudonaja textilis textilis, Oxyuranus microlepidotus and Demansia nuchalis affinis. A member of peptidase family S1.

Links to other databases:

BRENDA, EXPASY, KEGG, MEROPS, CAS registry number: 93389-45-8

References:

1.	Walker, F.J., Owen, W.G. and Esmon, C.T. Characterization of the prothrombin activator from the venom of Oxyuranus scutellatus scutellatus (taipan venom). Biochemistry 19 (1980) 1020–1023. [PMID: 6986908]
2.	Speijer, H., Govers-Reimslag, J.W., Zwaal, R.F. and Rosing, J. Prothrombin activation by an activator from the venom of Oxyuranus scutellatus (taipan snake). J. Biol. Chem. 261 (1986) 13258–13267. [PMID: 3531198]

[EC 3.4.21.60 created 1978 as EC 3.4.99.28, transferred 1992 to EC 3.4.21.60, modified 2010, modified 2011]

*EC

3.4.25.2

Accepted name:

HslU—HslV peptidase

Reaction:

ATP-dependent cleavage of peptide bonds with broad specificity.

Other name(s):

HslUV; HslV-HslU; HslV peptidase; ATP-dependent HslV-HslU proteinase; caseinolytic protease X; caseinolytic proteinase X; ClpXP ATP-dependent protease; ClpXP protease; ClpXP serine proteinase; Escherichia coli ClpXP serine proteinase; HslUV protease; HslUV proteinase; HslVU protease; HslVU proteinase; protease HslVU; proteinase HslUV

Comments:

The HslU subunit of the HslU—HslV complex functions as an ATP dependent ‘unfoldase’. The binding of ATP and its subsequent hydrolysis by HslU are essential for unfolding of protein substrates subsequently hydrolysed by HslV [5]. HslU recognizes the N-terminal part of its protein substrates and unfolds these before they are guided to HslV for hydrolysis [7]. In peptidase family T1.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, MEROPS, PDB

References:

1.	Wang, J., Rho, S.H., Park, H.H. and Eom, S.H. Correction of X-ray intensities from an HslV-HslU co-crystal containing lattice-translocation defects. Acta Crystallogr. D Biol. Crystallogr. 61 (2005) 932–941. [DOI] [PMID: 15983416]
2.	Nishii, W. and Takahashi, K. Determination of the cleavage sites in SulA, a cell division inhibitor, by the ATP-dependent HslVU protease from Escherichia coli. FEBS Lett. 553 (2003) 351–354. [DOI] [PMID: 14572649]
3.	Ramachandran, R., Hartmann, C., Song, H.K., Huber, R. and Bochtler, M. Functional interactions of HslV (ClpQ) with the ATPase HslU (ClpY). Proc. Natl. Acad. Sci. USA 99 (2002) 7396–7401. [DOI] [PMID: 12032294]
4.	Yoo, S.J., Seol, J.H., Shin, D.H., Rohrwild, M., Kang, M.S., Tanaka, K., Goldberg, A.L. and Chung, C.H. Purification and characterization of the heat shock proteins HslV and HslU that form a new ATP-dependent protease in Escherichia coli. J. Biol. Chem. 271 (1996) 14035–14040. [DOI] [PMID: 8662828]
5.	Yoo, S.J., Seol, J.H., Seong, I.S., Kang, M.S. and Chung, C.H. ATP binding, but not its hydrolysis, is required for assembly and proteolytic activity of the HslVU protease in Escherichia coli. Biochem. Biophys. Res. Commun. 238 (1997) 581–585. [DOI] [PMID: 9299555]
6.	Kanemori, M., Nishihara, K., Yanagi, H. and Yura, T. Synergistic roles of HslVU and other ATP-dependent proteases in controlling in vivo turnover of σ³² and abnormal proteins in Escherichia coli. J. Bacteriol. 179 (1997) 7219–7225. [DOI] [PMID: 9393683]
7.	Burton, R.E., Baker, T.A. and Sauer, R.T. Nucleotide-dependent substrate recognition by the AAA⁺ HslUV protease. Nat. Struct. Mol. Biol. 12 (2005) 245–251. [DOI] [PMID: 15696175]

[EC 3.4.25.2 created 2009, modified 2010]

*EC

3.5.1.100

Accepted name:

(R)-amidase

Reaction:

(1) (R)-piperazine-2-carboxamide + H₂O = (R)-piperazine-2-carboxylate + NH₃
(2) β-alaninamide + H₂O = β-alanine + NH₃

Other name(s):

R-stereospecific amidase; R-amidase

Systematic name:

(R)-piperazine-2-carboxamide amidohydrolase

Comments:

In addition (R)-piperidine-3-carboxamide is hydrolysed to (R)-piperidine-3-carboxylic acid and NH₃, and (R)-N-tert-butylpiperazine-2-carboxamide is hydrolysed to (R)-piperazine-2-carboxylic acid and tert-butylamine with lower activity. The enzyme does not act on the other amide substrates which are hydrolysed by EC 3.5.1.4 (amidase).

Links to other databases:

References:

1.	Komeda, H., Harada, H., Washika, S., Sakamoto, T., Ueda, M. and Asano, Y. A novel R-stereoselective amidase from Pseudomonas sp. MCI3434 acting on piperazine-2-tert-butylcarboxamide. Eur. J. Biochem. 271 (2004) 1580–1590. [DOI] [PMID: 15066183]

[EC 3.5.1.100 created 2009, modified 2011]

*EC

3.5.1.102

Accepted name:

2-amino-5-formylamino-6-ribosylaminopyrimidin-4(3H)-one 5′-monophosphate deformylase

Reaction:

2-amino-5-formylamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one + H₂O = 2,5-diamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one + formate

Other name(s):

ArfB

Systematic name:

2-amino-5-formylamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one amidohydrolase

Comments:

The enzyme catalyses the second step in archaeal riboflavin and 7,8-didemethyl-8-hydroxy-5-deazariboflavin biosynthesis. The first step is catalysed by EC 3.5.4.29 (GTP cyclohydrolase IIa). The bacterial enzyme, EC 3.5.4.25 (GTP cyclohydrolase II) catalyses both reactions.

Links to other databases:

References:

1.	Grochowski, L.L., Xu, H. and White, R.H. An iron(II) dependent formamide hydrolase catalyzes the second step in the archaeal biosynthetic pathway to riboflavin and 7,8-didemethyl-8-hydroxy-5-deazariboflavin. Biochemistry 48 (2009) 4181–4188. [DOI] [PMID: 19309161]

[EC 3.5.1.102 created 2010, modified 2011]

3.5.2.19

Accepted name:

streptothricin hydrolase

Reaction:

streptothricin-F + H₂O = streptothricin-F acid

Other name(s):

sttH (gene name)

Systematic name:

streptothricin-F hydrolase

Comments:

The enzyme also catalyses the hydrolysis of streptothricin-D to streptothricin-D acid [1]. The enzyme is responsible for streptothricin resistance in Streptomyces albulus and Streptomyces noursei [1,2].

Links to other databases:

References:

1.	Maruyama, C. and Hamano, Y. The biological function of the bacterial isochorismatase-like hydrolase SttH. Biosci. Biotechnol. Biochem. 73 (2009) 2494–2500. [DOI] [PMID: 19897889]
2.	Hamano, Y., Matsuura, N., Kitamura, M. and Takagi, H. A novel enzyme conferring streptothricin resistance alters the toxicity of streptothricin D from broad-spectrum to bacteria-specific. J. Biol. Chem. 281 (2006) 16842–16848. [DOI] [PMID: 16641084]

[EC 3.5.2.19 created 2011]

*EC

3.5.4.25

Accepted name:

GTP cyclohydrolase II

Reaction:

GTP + 4 H₂O = formate + 2,5-diamino-6-hydroxy-4-(5-phospho-D-ribosylamino)pyrimidine + 2 phosphate

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

Other name(s):

guanosine triphosphate cyclohydrolase II; GTP-8-formylhydrolase; ribA (gene name); GTP 7,8-8,9-dihydrolase (diphosphate-forming)

Systematic name:

GTP 7,8-8,9-dihydrolase (formate-releasing, phosphate-releasing)

Comments:

The enzyme, found in prokaryotes and some eukaryotes, hydrolytically cleaves the C-N bond at positions 8 and 9 of GTP guanine, followed by a subsequent hydrolytic attack at the base, which liberates formate, and cleavage of the α-β phosphodiester bond of the triphosphate to form diphosphate. The enzyme continues with a slow cleavage of the diphosphate to form two phosphate ions. The enzyme requires zinc and magnesium ions for the cleavage reactions at the GTP guanine and triphosphate sites, respectively. It is one of the enzymes required for flavin biosynthesis in many bacterial species, lower eukaryotes, and plants. cf. EC 3.5.4.16, GTP cyclohydrolase I, EC 3.5.4.29, GTP cyclohydrolase IIa, and EC 3.5.4.39, GTP cyclohydrolase IV.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 56214-35-8

References:

1.	Foor, F. and Brown, G.M. Purification and properties of guanosine triphosphate cyclohydrolase II from Escherichia coli. J. Biol. Chem. 250 (1975) 3545–3551. [PMID: 235552]
2.	Ritz, H., Schramek, N., Bracher, A., Herz, S., Eisenreich, W., Richter, G. and Bacher, A. Biosynthesis of riboflavin: studies on the mechanism of GTP cyclohydrolase II. J. Biol. Chem. 276 (2001) 22273–22277. [DOI] [PMID: 11301327]
3.	Schramek, N., Bracher, A. and Bacher, A. Biosynthesis of riboflavin. Single turnover kinetic analysis of GTP cyclohydrolase II. J. Biol. Chem. 276 (2001) 44157–44162. [DOI] [PMID: 11553632]
4.	Ren, J., Kotaka, M., Lockyer, M., Lamb, H.K., Hawkins, A.R. and Stammers, D.K. GTP cyclohydrolase II structure and mechanism. J. Biol. Chem. 280 (2005) 36912–36919. [DOI] [PMID: 16115872]
5.	Smith, M.M., Beaupre, B.A., Fourozesh, D.C., Meneely, K.M., Lamb, A.L. and Moran, G.R. Finding ways to relax: a revisionistic analysis of the chemistry of E. coli GTP cyclohydrolase II. Biochemistry 60 (2021) 3027–3039. [DOI] [PMID: 34569786]

[EC 3.5.4.25 created 1984, modified 2011, modified 2022]

*EC

3.5.4.26

Accepted name:

diaminohydroxyphosphoribosylaminopyrimidine deaminase

Reaction:

2,5-diamino-6-hydroxy-4-(5-phospho-D-ribosylamino)pyrimidine + H₂O = 5-amino-6-(5-phospho-D-ribosylamino)uracil + NH₃

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

Systematic name:

2,5-diamino-6-hydroxy-4-(5-phospho-D-ribosylamino)pyrimidine 2-aminohydrolase

Comments:

The substrate is the product of EC 3.5.4.25 GTP cyclohydrolase II.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 68994-19-4

References:

1.	Burrows, R.B. and Brown, G.M. Presence of Escherichia coli of a deaminase and a reductase involved in biosynthesis of riboflavin. J. Bacteriol. 136 (1978) 657–667. [PMID: 30756]

[EC 3.5.4.26 created 1984, modified 2011]

*EC

3.5.4.29

Accepted name:

GTP cyclohydrolase IIa

Reaction:

GTP + 3 H₂O = 2-amino-5-formylamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one + 2 phosphate

For diagram of reaction, click here

Systematic name:

GTP 8,9-hydrolase (phosphate-forming)

Comments:

Requires Mg²⁺. This enzyme catalyses the hydrolysis of the imidazole ring of guanosine 5′-triphosphate, N⁷-methylguanosine 5′-triphosphate or inosine 5′-triphosphate. Xanthosine 5′-triphosphate and ATP are not substrates. It also catalyses the hydrolysis of diphosphate to form two equivalents of phosphate. Unlike GTP cyclohydrolase II (EC 3.5.4.25), this enzyme does not release formate, but does hydrolyse the diphosphate from GTP to phosphate.

Links to other databases:

References:

1.	Graham, D.E., Xu, H. and White, R.H. A member of a new class of GTP cyclohydrolases produces formylaminopyrimidine nucleotide monophosphates. Biochemistry 41 (2002) 15074–15084. [DOI] [PMID: 12475257]

[EC 3.5.4.29 created 2003, modified 2011]

3.5.99.8

Accepted name:

5-nitroanthranilic acid aminohydrolase

Reaction:

5-nitroanthranilate + H₂O = 5-nitrosalicylate + NH₃

Other name(s):

naaA (gene name); 5NAA deaminase

Systematic name:

5-nitroanthranilate amidohydrolase

Comments:

The enzyme catalyses the initial step in biodegradation of 5-nitroanthranilic acid by Bradyrhizobium sp. strain JS329.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, KEGG, PDB

References:

1.	Qu, Y. and Spain, J.C. Biodegradation of 5-nitroanthranilic acid by Bradyrhizobium sp. strain JS329. Appl. Environ. Microbiol. 76 (2010) 1417–1422. [DOI] [PMID: 20081004]

[EC 3.5.99.8 created 2011]

3.7.1.12

Accepted name:

cobalt-precorrin 5A hydrolase

Reaction:

cobalt-precorrin-5A + H₂O = cobalt-precorrin-5B + acetaldehyde + 2 H⁺

For diagram of anaerobic corrin biosynthesis (part 1), click here

Other name(s):

CbiG

Systematic name:

cobalt-precorrin 5A acylhydrolase

Comments:

This enzyme hydrolyses the ring A acetate δ-lactone of cobalt-precorrin-5A resulting in the loss of the C-20 carbon and its attached methyl group in the form of acetaldehyde. This is a key reaction in the contraction of the porphyrin-type tetrapyrrole ring and its conversion to a corrin ring in the anaerobic (early cobalt insertion) adenosylcobalamin biosynthesis pathway.

Links to other databases:

References:

1.	Kajiwara, Y., Santander, P.J., Roessner, C.A., Perez, L.M. and Scott, A.I. Genetically engineered synthesis and structural characterization of cobalt-precorrin 5A and -5B, two new intermediates on the anaerobic pathway to vitamin B₁₂: definition of the roles of the CbiF and CbiG enzymes. J. Am. Chem. Soc. 128 (2006) 9971–9978. [DOI] [PMID: 16866557]
2.	Moore, S.J., Lawrence, A.D., Biedendieck, R., Deery, E., Frank, S., Howard, M.J., Rigby, S.E. and Warren, M.J. Elucidation of the anaerobic pathway for the corrin component of cobalamin (vitamin B₁₂). Proc. Natl. Acad. Sci. USA 110 (2013) 14906–14911. [DOI] [PMID: 23922391]

[EC 3.7.1.12 created 2010]

3.7.1.13

Accepted name:

2-hydroxy-6-oxo-6-(2-aminophenyl)hexa-2,4-dienoate hydrolase

Reaction:

(2E,4E)-6-(2-aminophenyl)-2-hydroxy-6-oxohexa-2,4-dienoate + H₂O = anthranilate + (2E)-2-hydroxypenta-2,4-dienoate

Other name(s):

CarC

Systematic name:

(2E,4E)-6-(2-aminophenyl)-2-hydroxy-6-oxohexa-2,4-dienoate acylhydrolase

Comments:

This enzyme catalyses the third step in the aerobic degradation pathway of carbazole. The effect of the presence of an amino group or hydroxyl group at the 2-position of the substrate is small. The enzyme has no cofactor requirement [2].

Links to other databases:

References:

1.	Nojiri, H., Taira, H., Iwata, K., Morii, K., Nam, J.W., Yoshida, T., Habe, H., Nakamura, S., Shimizu, K., Yamane, H. and Omori, T. Purification and characterization of meta-cleavage compound hydrolase from a carbazole degrader Pseudomonas resinovorans strain CA10. Biosci. Biotechnol. Biochem. 67 (2003) 36–45. [DOI] [PMID: 12619671]
2.	Riddle, R.R., Gibbs, P.R., Willson, R.C. and Benedik, M.J. Purification and properties of 2-hydroxy-6-oxo-6-(2′-aminophenyl)hexa-2,4-dienoic acid hydrolase involved in microbial degradation of carbazole. Protein Expr. Purif. 28 (2003) 182–189. [DOI] [PMID: 12651123]

[EC 3.7.1.13 created 2010]

*EC

3.13.1.1

Accepted name:

UDP-sulfoquinovose synthase

Reaction:

UDP-α-D-sulfoquinovopyranose + H₂O = UDP-α-D-glucose + sulfite

For diagram of UDP-glucose, UDP-galactose and UDP-glucuronate biosynthesis, click here

Other name(s):

sulfite:UDP-glucose sulfotransferase; UDPsulfoquinovose synthase; UDP-6-sulfo-6-deoxyglucose sulfohydrolase

Systematic name:

UDP-6-sulfo-6-deoxy-α-D-glucose sulfohydrolase

Comments:

Requires NAD⁺, which appears to oxidize UDP-α-D-glucose to UDP-4-dehydroglucose, which dehydrates to UDP-4-dehydro-6-deoxygluc-5-enose, to which sulfite is added. The reaction is completed when the substrate is rehydrogenated at C-4. The enzyme from Arabidopsis thaliana is specific for UDP-Glc and sulfite.

Links to other databases:

References:

1.	Essigmann, B., Gler, S., Narang, R.A., Linke, D. and Benning, C. Phosphate availability affects the thylakoid lipid composition and the expression of SQD1, a gene required for sulfolipid biosynthesis in Arabidopsis thaliana. Proc. Natl. Acad. Sci. USA 95 (1998) 1950–1955. [DOI] [PMID: 9465123]
2.	Essigmann, B., Hespenheide, B.M., Kuhn, L.A. and Benning, C. Prediction of the active-site structure and NAD⁺ binding in SQD1, a protein essential for sulfolipid biosynthesis in Arabidopsis. Arch. Biochem. Biophys. 369 (1999) 30–41. [DOI] [PMID: 10462438]
3.	Mulichak, A.M., Theisen, M.J., Essigmann, B., Benning, C. and Garavito, R.M. Crystal structure of SQD1, an enzyme involved in the biosynthesis of the plant sulfolipid headgroup donor UDP-sulfoquinovose. Proc. Natl. Acad. Sci. USA 96 (1999) 13097–13102. [DOI] [PMID: 10557279]
4.	Sanda, S., Leustek, T., Theisen, M., Garavito, R.M. and Benning, C. Recombinant Arabidopsis SQD1 converts UDP-glucose and sulfite to the sulfolipid head group precursor UDP-sulfoquinovose in vitro. J. Biol. Chem. 276 (2001) 3941–3946. [DOI] [PMID: 11073956]

[EC 3.13.1.1 created 2001, modified 2010]

*EC

4.1.2.10

Accepted name:

(R)-mandelonitrile lyase

Reaction:

(R)-mandelonitrile = cyanide + benzaldehyde

Other name(s):

(R)-oxynitrilase; oxynitrilase; D-oxynitrilase; D-α-hydroxynitrile lyase; mandelonitrile benzaldehyde-lyase; PaHNL; AtHNL; PhaMDL; (R)-HNL; (R)-PeHNL; (R)-hydroxynitrile lyase; R-selective hydroxynitrile lyase; R-selective HNL; (R)-(+)-mandelonitrile lyase

Systematic name:

(R)-mandelonitrile benzaldehyde-lyase (cyanide-forming)

Comments:

A variety of enzymes from different sources and with different properties. Some are flavoproteins, others are not. Active towards a number of aromatic and aliphatic hydroxynitriles (cyanohydrins).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9024-43-5

References:

1.	Ueatrongchit, T., Kayo, A., Komeda, H., Asano, Y. and H-Kittikun, A. Purification and characterization of a novel (R)-hydroxynitrile lyase from Eriobotrya japonica (Loquat). Biosci. Biotechnol. Biochem. 72 (2008) 1513–1522. [DOI] [PMID: 18540101]
2.	Lin, G., Han, S. and Li, Z. Enzymic synthesis of (R)-cyanohydrins by three (R)-oxynitrilase sources in micro-aqueous organic medium. Tetrahedron 55 (1999) 3531–3540.
3.	de Gonzalo, G., Brieva, R. and Gotor, V. (R)-Oxynitrilase-catalyzed transformation of ω-hydroxyalkanals. J. Mol. Catal. B 19-20 (2002) 223–230.
4.	Ueatrongchit, T., Tamura, K., Ohmiya, T., H-Kittikun, A. and Asano, Y. Hydroxynitrile lyase from Passiflora edulis. Purification, characteristics and application in asymmetric synthesis of (R)-mandelonitrile. Enzyme Microb. Technol. 46 (2010) 456–465. [PMID: 25919621]
5.	Andexer, J., von Langermann, J., Mell, A., Bocola, M., Kragl, U., Eggert, T. and Pohl, M. An R-selective hydroxynitrile lyase from Arabidopsis thaliana with an α/β-hydrolase fold. Angew. Chem. Int. Ed. Engl. 46 (2007) 8679–8681. [DOI] [PMID: 17907254]
6.	Guterl, J.K., Andexer, J.N., Sehl, T., von Langermann, J., Frindi-Wosch, I., Rosenkranz, T., Fitter, J., Gruber, K., Kragl, U., Eggert, T. and Pohl, M. Uneven twins: comparison of two enantiocomplementary hydroxynitrile lyases with α/β-hydrolase fold. J. Biotechnol. 141 (2009) 166–173. [DOI] [PMID: 19433222]

[EC 4.1.2.10 created 1961, modified 1999, modified 2011]

4.1.2.37

Deleted entry:

hydroxynitrilase. Now covered by EC 4.1.2.46 [aliphatic (R)-hydroxynitrile lyase] and EC 4.1.2.47 [(S)-hydroxynitrile ketone-lyase (cyanide forming)]

[EC 4.1.2.37 created 1992 (EC 4.1.2.39 created 1999, incorporated 2007), deleted 2011]

*EC

4.1.2.45

Accepted name:

trans-o-hydroxybenzylidenepyruvate hydratase-aldolase

Reaction:

(3E)-4-(2-hydroxyphenyl)-2-oxobut-3-enoate + H₂O = salicylaldehyde + pyruvate

For diagram of naphthalene metabolism, click here

Glossary:

(3E)-4-(2-hydroxyphenyl)-2-oxobut-3-enoate = (E)-2′-hydroxybenzylidenepyruvate
salicylaldehyde = 2-hydroxybenzaldehyde

Other name(s):

2′-hydroxybenzalpyruvate aldolase; NsaE; tHBPA hydratase-aldolase

Systematic name:

(3E)-4-(2-hydroxyphenyl)-2-oxobut-3-enoate hydro-lyase

Comments:

This enzyme is involved in naphthalene degradation. The enzyme catalyses a retro-aldol reaction in vitro, and it accepts a broad range of aldehydes and 4-substituted 2-oxobut-3-enoates as substrates [4].

Links to other databases:

References:

1.	Kuhm, A.E., Knackmuss, H.J. and Stolz, A. Purification and properties of 2′-hydroxybenzalpyruvate aldolase from a bacterium that degrades naphthalenesulfonates. J. Biol. Chem. 268 (1993) 9484–9489. [PMID: 8486638]
2.	Keck, A., Conradt, D., Mahler, A., Stolz, A., Mattes, R. and Klein, J. Identification and functional analysis of the genes for naphthalenesulfonate catabolism by Sphingomonas xenophaga BN6. Microbiology 152 (2006) 1929–1940. [DOI] [PMID: 16804169]
3.	Eaton, R.W. Organization and evolution of naphthalene catabolic pathways: sequence of the DNA encoding 2-hydroxychromene-2-carboxylate isomerase and trans-o-hydroxybenzylidenepyruvate hydratase-aldolase from the NAH7 plasmid. J. Bacteriol. 176 (1994) 7757–7762. [DOI] [PMID: 8002605]
4.	Eaton, R.W. trans-o-Hydroxybenzylidenepyruvate hydratase-aldolase as a biocatalyst. Appl. Environ. Microbiol. 66 (2000) 2668–2672. [DOI] [PMID: 10831455]

[EC 4.1.2.45 created 2010, modified 2011]

4.1.2.46

Accepted name:

aliphatic (R)-hydroxynitrile lyase

Reaction:

(2R)-2-hydroxy-2-methylbutanenitrile = cyanide + butan-2-one

Other name(s):

(R)-HNL; (R)-oxynitrilase; (R)-hydroxynitrile lyase; LuHNL

Systematic name:

(2R)-2-hydroxy-2-methylbutanenitrile butan-2-one-lyase (cyanide-forming)

Comments:

The enzyme contains Zn²⁺ [1]. The enzyme catalyses the stereoselective synthesis of aliphatic (R)-cyanohydrins [1]. No activity towards mandelonitrile and 4-hydroxymandelonitrile [5]. Natural substrates for the (R)-oxynitrilase from Linum usitatissimum are acetone and butan-2-one, which are the building blocks of the cyanogen glycosides in Linum, linamarin and lotaustralin, or linustatin and neolinustatin, respectively [4].

Links to other databases:

References:

1.	Trummler, K., Roos, J., Schwaneberg, U., Effenberger, F., Förster, S., Pfizenmaier, K. and Wajant, H. Expression of the Zn²⁺-containing hydroxynitrile lyase from flax (Linum usitatissimum) in Pichia pastoris— utilization of the recombinant enzyme for enzymatic analysis and site-directed mutagenesis. Plant Sci. 139 (1998) 19–27.
2.	Trummler, K. and Wajant, H. Molecular cloning of acetone cyanohydrin lyase from flax (Linum usitatissimum). Definition of a novel class of hydroxynitrile lyases. J. Biol. Chem. 272 (1997) 4770–4774. [DOI] [PMID: 9030531]
3.	Albrecht, J., Jansen, I.and Kula, M.R. Improved purification of an (R)-oxynitrilase from Linum usitatissimum (flax) and investigation of the substrate range. Biotechnol. Appl. Biochem. 17 (1993) 191–203. [PMID: 8387315]
4.	Xu, L.-L., Singh, B.K. and Conn, E.E. Purification and characterization of acetone cyanohydrin lyase from Linum usitatissimum. Arch. Biochem. Biophys. 263 (1988) 256–263. [DOI] [PMID: 3377504]
5.	Cabirol, F.L., Tan, P.L., Tay, B., Cheng, S., Hanefeld, U. and Sheldon, R.A. Linum usitatissimum hydroxynitrile lyase cross-linked enzyme aggregates: a recyclable enantioselective catalyst. Adv. Synth. Catal. 350 (2008) 2329–2338.
6.	Breithaupt, H., Pohl, M., Bönigk, W., Heim, P., Schimz, K.-L. and Kula, M.-R. Cloning and expression of (R)-hydroxynitrile lyase from Linum usitatissimum (flax). J. Mol. Catal. B 6 (1999) 315–332. [DOI]

[EC 4.1.2.46 created 2011]

4.1.2.47

Accepted name:

(S)-hydroxynitrile lyase

Reaction:

(1) an aliphatic (S)-hydroxynitrile = cyanide + an aliphatic aldehyde or ketone
(2) an aromatic (S)-hydroxynitrile = cyanide + an aromatic aldehyde

Other name(s):

(S)-cyanohydrin producing hydroxynitrile lyase; (S)-oxynitrilase; (S)-HbHNL; (S)-MeHNL; hydroxynitrile lyase; oxynitrilase; HbHNL; MeHNL; (S)-selective hydroxynitrile lyase; (S)-cyanohydrin carbonyl-lyase (cyanide forming)

Systematic name:

(S)-cyanohydrin lyase (cyanide-forming)

Comments:

Hydroxynitrile lyases catalyses the the cleavage of hydroxynitriles into cyanide and the corresponding aldehyde or ketone. In nature the liberation of cyanide serves as a defense mechanism against herbivores and microbial attack in plants. In vitro the enzymes from Manihot esculenta and Hevea brasiliensis accept a broad range of aliphatic and aromatic carbonyl compounds as substrates and catalyse the formation of (S)-hydroxynitriles [1,10].

Links to other databases:

References:

1.	Förster, S., Roos, J., Effenberger, F., Wajant, H. and Sprauer, A. The first recombinant hydroxynitrile lyase and its application in the synthesis of (S)-cyanohydrins. Angew. Chem. Int. Ed. 35 (1996) 437–439.
2.	Bühler, H., Effenberger, F., Förster, S., Roos, J. and Wajant, H. Substrate specificity of mutants of the hydroxynitrile lyase from Manihot esculenta. ChemBioChem 4 (2003) 211–216. [DOI] [PMID: 12616635]
3.	Semba, H., Dobashi, Y. and Matsui, T. Expression of hydroxynitrile lyase from Manihot esculenta in yeast and its application in (S)-mandelonitrile production using an immobilized enzyme reactor. Biosci. Biotechnol. Biochem. 72 (2008) 1457–1463. [PMID: 18540112]
4.	Avi, M., Wiedner, R.M., Griengl, H. and Schwab, H. Improvement of a stereoselective biocatalytic synthesis by substrate and enzyme engineering: 2-hydroxy-(4′-oxocyclohexyl)acetonitrile as the model. Chemistry 14 (2008) 11415–11422. [DOI] [PMID: 19006143]
5.	von Langermann, J., Guterl, J.K., Pohl, M., Wajant, H. and Kragl, U. Hydroxynitrile lyase catalyzed cyanohydrin synthesis at high pH-values. Bioprocess Biosyst. Eng. 31 (2008) 155–161. [DOI] [PMID: 18204865]
6.	Schmidt, A., Gruber, K., Kratky, C. and Lamzin, V.S. Atomic resolution crystal structures and quantum chemistry meet to reveal subtleties of hydroxynitrile lyase catalysis. J. Biol. Chem. 283 (2008) 21827–21836. [DOI] [PMID: 18524775]
7.	Gartler, G., Kratky, C. and Gruber, K. Structural determinants of the enantioselectivity of the hydroxynitrile lyase from Hevea brasiliensis. J. Biotechnol. 129 (2007) 87–97. [DOI] [PMID: 17250917]
8.	Wagner, U.G., Schall, M., Hasslacher, M., Hayn, M., Griengl, H., Schwab, H. and Kratky, C. Crystallization and preliminary X-ray diffraction studies of a hydroxynitrile lyase from Hevea brasiliensis. Acta Crystallogr. D Biol. Crystallogr. 52 (1996) 591–593. [DOI] [PMID: 15299689]
9.	Schmidt, M., Herve, S., Klempier, N. and Griengl, H. Preparation of optically active cyanohydrins using the (S)-hydroxynitrile lyase from Hevea brasiliensis. Tetrahedron 52 (1996) 7833–7840.
10.	Klempier, N. and Griengl, H. Aliphatic (S)-cyanohydrins by enzyme catalyzed synthesis. Tetrahedron Lett. 34 (1993) 4769–4772.

[EC 4.1.2.47 created 2011]

*EC

4.1.3.14

Accepted name:

L-erythro-3-hydroxyaspartate aldolase

Reaction:

L-erythro-3-hydroxy-aspartate = glycine + glyoxylate

Other name(s):

L-erythro-β-hydroxyaspartate aldolase; L-erythro-β-hydroxyaspartate glycine-lyase; erythro-3-hydroxy-L_s-aspartate glyoxylate-lyase

Systematic name:

L-erythro-3-hydroxy-aspartate glyoxylate-lyase (glycine-forming)

Comments:

A pyridoxal-phosphate protein. The enzyme, purified from the bacterium Paracoccus denitrificans NCIMB 8944, is strictly specific for the L-erythro stereoisomer of 3-hydroxyaspartate. Different from EC 4.1.3.41, erythro-3-hydroxy-D-aspartate aldolase. Requires a divalent cation.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 37290-64-5

References:

1.	Gibbs, R.G. and Morris, J.G. Assay and properties of β-hydroxyaspartate aldolase from Micrococcus denitrificans. Biochim. Biophys. Acta 85 (1964) 501–503. [PMID: 14194868]

[EC 4.1.3.14 created 1972, modified 2011]

*EC

4.1.3.36

Accepted name:

1,4-dihydroxy-2-naphthoyl-CoA synthase

Reaction:

4-(2-carboxyphenyl)-4-oxobutanoyl-CoA = 1,4-dihydroxy-2-naphthoyl-CoA + H₂O

For diagram of vitamin-K biosynthesis, click here

Other name(s):

naphthoate synthase; 1,4-dihydroxy-2-naphthoate synthase; dihydroxynaphthoate synthase; o-succinylbenzoyl-CoA 1,4-dihydroxy-2-naphthoate-lyase (cyclizing); MenB; o-succinylbenzoyl-CoA dehydratase (cyclizing)

Systematic name:

4-(2-carboxyphenyl)-4-oxobutanoyl-CoA dehydratase (cyclizing)

Comments:

This enzyme is involved in the synthesis of 1,4-dihydroxy-2-naphthoate, a branch point metabolite leading to the biosynthesis of menaquinone (vitamin K₂, in bacteria), phylloquinone (vitamin K₁ in plants), and many plant pigments. The coenzyme A group is subsequently removed from the product by EC 3.1.2.28, 1,4-dihydroxy-2-naphthoyl-CoA hydrolase.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 61328-42-5

References:

1.	Meganathan, R. and Bentley, R. Menaquinone (vitamin K₂) biosynthesis: conversion of o-succinylbenzoic acid to 1,4-dihydroxy-2-naphthoic acid by Mycobacterium phlei enzymes. J. Bacteriol. 140 (1979) 92–98. [PMID: 500558]
2.	Kolkmann, R. and Leistner, E. 4-(2′-Carboxyphenyl)-4-oxobutyryl coenzyme A ester, an intermediate in vitamin K₂ (menaquinone) biosynthesis. Z. Naturforsch. C: Sci. 42 (1987) 1207–1214. [PMID: 2966501]
3.	Johnson, T.W., Shen, G., Zybailov, B., Kolling, D., Reategui, R., Beauparlant, S., Vassiliev, I.R., Bryant, D.A., Jones, A.D., Golbeck, J.H. and Chitnis, P.R. Recruitment of a foreign quinone into the A(1) site of photosystem I. I. Genetic and physiological characterization of phylloquinone biosynthetic pathway mutants in Synechocystis sp. PCC 6803. J. Biol. Chem. 275 (2000) 8523–8530. [DOI] [PMID: 10722690]
4.	Truglio, J.J., Theis, K., Feng, Y., Gajda, R., Machutta, C., Tonge, P.J. and Kisker, C. Crystal structure of Mycobacterium tuberculosis MenB, a key enzyme in vitamin K₂ biosynthesis. J. Biol. Chem. 278 (2003) 42352–42360. [DOI] [PMID: 12909628]

[EC 4.1.3.36 created 1992, modified 2010]

4.1.3.41

Accepted name:

3-hydroxy-D-aspartate aldolase

Reaction:

(1) threo-3-hydroxy-D-aspartate = glycine + glyoxylate
(2) D-erythro-3-hydroxyaspartate = glycine + glyoxylate

Other name(s):

D-3-hydroxyaspartate aldolase

Systematic name:

3-hydroxy-D-aspartate glyoxylate-lyase (glycine-forming)

Comments:

A pyridoxal-phosphate protein. The enzyme, purified from the bacterium Paracoccus denitrificans IFO 13301, is strictly D-specific as to the α-position of the substrate, but accepts both the threo and erythro forms at the β-position. The erythro form is a far better substrate (about 100-fold). The enzyme can also accept D-allothreonine, D-threonine, erythro-3-phenyl-D-serine and threo-3-phenyl-D-serine. Different from EC 4.1.3.14, erythro-3-hydroxy-L-aspartate aldolase. Requires a divalent cation, such as Mg²⁺, Mn²⁺ or Co²⁺.

Links to other databases:

References:

1.	Liu, J.Q., Dairi, T., Itoh, N., Kataoka, M. and Shimizu, S. A novel enzyme, D-3-hydroxyaspartate aldolase from Paracoccus denitrificans IFO 13301: purification, characterization, and gene cloning. Appl. Microbiol. Biotechnol. 62 (2003) 53–60. [DOI] [PMID: 12835921]

[EC 4.1.3.41 created 2011]

*EC

4.1.99.5

Accepted name:

aldehyde oxygenase (deformylating)

Reaction:

a long-chain aldehyde + O₂ + 2 NADPH + 2 H⁺ = an alkane + formate + H₂O + 2 NADP⁺

Glossary:

a long-chain aldehyde = an aldehyde derived from a fatty acid with an aliphatic chain of 13-22 carbons.

Other name(s):

decarbonylase; aldehyde decarbonylase; octadecanal decarbonylase; octadecanal alkane-lyase

Systematic name:

a long-chain aldehyde alkane-lyase

Comments:

Contains a diiron center. Involved in the biosynthesis of alkanes. The enzyme from the cyanobacterium Nostoc punctiforme PCC 73102 is only active in vitro in the presence of ferredoxin, ferredoxin reductase and NADPH, and produces mostly C₁₅ and C₁₇ alkanes [2,3]. The enzyme from pea (Pisum sativum) produces alkanes of chain length C₁₈ to C₃₂ and is inhibited by metal-chelating agents [1]. The substrate for this enzyme is formed by EC 1.2.1.80, acyl-[acyl-carrier protein] reductase.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 94185-90-7

References:

1.	Cheesbrough, T.M. and, K olattukudy, P.E. Alkane biosynthesis by decarbonylation of aldehydes catalyzed by a particulate preparation from Pisum sativum. Proc. Natl. Acad. Sci. USA 81 (1984) 6613–6617. [DOI] [PMID: 6593720]
2.	Schirmer, A., Rude, M.A., Li, X., Popova, E. and del Cardayre, S.B. Microbial biosynthesis of alkanes. Science 329 (2010) 559–562. [DOI] [PMID: 20671186]
3.	Warui, D.M., Li, N., Nørgaard, H., Krebs, C., Bollinger, J.M. and Booker, S.J. Detection of formate, rather than carbon monoxide, as the stoichiometric coproduct in conversion of fatty aldehydes to alkanes by a cyanobacterial aldehyde decarbonylase. J. Am. Chem. Soc. 133 (2011) 3316–3319. [DOI] [PMID: 21341652]
4.	Li, N., Chang, W.C., Warui, D.M., Booker, S.J., Krebs, C. and Bollinger, J.M., Jr. Evidence for only oxygenative cleavage of aldehydes to alk(a/e)nes and formate by cyanobacterial aldehyde decarbonylases. Biochemistry 51 (2012) 7908–7916. [DOI] [PMID: 22947199]

[EC 4.1.99.5 created 1989, modified 2011, modified 2013]

*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]

4.2.1.121

Accepted name:

colneleate synthase

Reaction:

(9S,10E,12Z)-9-hydroperoxyoctadeca-10,12-dienoate = (8E)-9-[(1E,3Z)-nona-1,3-dien-1-yloxy]non-8-enoate + H₂O

Glossary:

colneleate = (8E)-9-[(1E,3Z)-nona-1,3-dien-1-yloxy]non-8-enoate

Other name(s):

9-divinyl ether synthase; 9-DES; CYP74D; CYP74D1; CYP74 cytochrome P-450; DES1; (8E)-9-[(1E,3E)-nona-1,3-dien-1-yloxy]non-8-enoate synthase

Systematic name:

(9S,10E,12Z)-9-hydroperoxyoctadeca-10,12-dienoate hydro-lyase

Comments:

A heme-thiolate protein (P-450) [2]. It catalyses the selective removal of pro-R hydrogen at C-8 in the biosynthesis of colneleic acid [4]. It forms also (8E)-9-[(1E,3Z,6Z)-nona-1,3,6-trien-1-yloxy]non-8-enoic acid (i.e. colnelenate) from (9S,10E,12Z,15Z)-9-hydroperoxy-10,12,15-octadecatrienoate. The corresponding 13-hydroperoxides are poor substrates [1,3]. The divinyl ethers colneleate and colnelenate have antimicrobial activity.

Links to other databases:

References:

1.	Stumpe, M., Kandzia, R., Gobel, C., Rosahl, S. and Feussner, I. A pathogen-inducible divinyl ether synthase (CYP74D) from elicitor-treated potato suspension cells. FEBS Lett. 507 (2001) 371–376. [DOI] [PMID: 11696374]
2.	Itoh, A. and Howe, G.A. Molecular cloning of a divinyl ether synthase. Identification as a CYP74 cytochrome P-450. J. Biol. Chem. 276 (2001) 3620–3627. [DOI] [PMID: 11060314]
3.	Fammartino, A., Cardinale, F., Gobel, C., Mene-Saffrane, L., Fournier, J., Feussner, I. and Esquerre-Tugaye, M.T. Characterization of a divinyl ether biosynthetic pathway specifically associated with pathogenesis in tobacco. Plant Physiol. 143 (2007) 378–388. [DOI] [PMID: 17085514]
4.	Hamberg, M. Hidden stereospecificity in the biosynthesis of divinyl ether fatty acids. FEBS J. 272 (2005) 736–743. [DOI] [PMID: 15670154]

[EC 4.2.1.121 created 2011, modified 2014]

*EC

4.2.2.21

Accepted name:

chondroitin-sulfate-ABC exolyase

Reaction:

Exolytic removal of Δ⁴-unsaturated disaccharide residues from the non-reducing ends of both polymeric chondroitin/dermatan sulfates and their oligosaccharide fragments.

For diagram of reaction click here

Glossary:

chondroitin sulfate A = chondroitin 4-sulfate
chondroitin sulfate B = dermatan sulfate
chondroitin sulfate C = chondroitin 6-sulfate
For the nomenclature of glycoproteins, glycopeptides and peptidoglycans, click here

Other name(s):

chondroitinase (ambiguous); chondroitin ABC eliminase (ambiguous); chondroitinase ABC (ambiguous); chondroitin ABC lyase (ambiguous); chondroitin sulfate ABC lyase (ambiguous); ChS ABC lyase (ambiguous); chondroitin sulfate ABC exoeliminase; chondroitin sulfate ABC exolyase; ChS ABC lyase II

Systematic name:

chondroitin-sulfate-ABC exolyase

Comments:

This enzyme degrades a variety of glycosaminoglycans of the chondroitin-sulfate- and dermatan-sulfate type. Chondroitin sulfate, chondroitin-sulfate proteoglycan and dermatan sulfate are the best substrates but the enzyme can also act on hyaluronan at a much lower rate. Keratan sulfate, heparan sulfate and heparin are not substrates. The related enzyme EC 4.2.2.20, chondroitin-sulfate-ABC endolyase, has the same substrate specificity but produces a mixture of oligosaccharides of different sizes that are ultimately degraded to tetra- and disaccharides [4]. Both enzymes act by the removal of a relatively acidic C-5 proton of the uronic acid followed by the elimination of a 4-linked hexosamine, resulting in the formation of an unsaturated C⁴—C⁵ bond on the hexuronic acid moiety of the products [4,6].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 1000607-06-6

References:

1.	Yamagata, T., Saito, H., Habuchi, O. and Suzuki, S. Purification and properties of bacterial chondroitinases and chondrosulfatases. J. Biol. Chem. 243 (1968) 1523–1535. [PMID: 5647268]
2.	Saito, H., Yamagata, T. and Suzuki, S. Enzymatic methods for the determination of small quantities of isomeric chondroitin sulfates. J. Biol. Chem. 243 (1968) 1536–1542. [PMID: 4231029]
3.	Suzuki, S., Saito, H., Yamagata, T., Anno, K., Seno, N., Kawai, Y. and Furuhashi, T. Formation of three types of disulfated disaccharides from chondroitin sulfates by chondroitinase digestion. J. Biol. Chem. 243 (1968) 1543–1550. [PMID: 5647269]
4.	Hamai, A., Hashimoto, N., Mochizuki, H., Kato, F., Makiguchi, Y., Horie, K. and Suzuki, S. Two distinct chondroitin sulfate ABC lyases. An endoeliminase yielding tetrasaccharides and an exoeliminase preferentially acting on oligosaccharides. J. Biol. Chem. 272 (1997) 9123–9130. [DOI] [PMID: 9083041]
5.	Huckerby, T.N., Nieduszynski, I.A., Giannopoulos, M., Weeks, S.D., Sadler, I.H. and Lauder, R.M. Characterization of oligosaccharides from the chondroitin/dermatan sulfates. ¹H-NMR and ¹³C-NMR studies of reduced trisaccharides and hexasaccharides. FEBS J. 272 (2005) 6276–6286. [DOI] [PMID: 16336265]
6.	Zhang, Z., Park, Y., Kemp, M.M., Zhao, W., Im, A.R., Shaya, D., Cygler, M., Kim, Y.S. and Linhardt, R.J. Liquid chromatography-mass spectrometry to study chondroitin lyase action pattern. Anal. Biochem. 385 (2009) 57–64. [DOI] [PMID: 18992215]

[EC 4.2.2.21 created 2006 (EC 4.2.2.4 created 1972, part-incorporated 2006 (EC 4.2.99.6 created 1965, part incorporated 1976)), modified 2010]

4.2.3.55

Accepted name:

(S)-β-bisabolene synthase

Reaction:

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

For diagram of bisabolene biosynthesis, click here, for diagram of bisabolene biosynthesis, click here and for diagram of bisabolene and macrocarpene biosynthesis, click here

Systematic name:

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

Comments:

The synthesis of (S)-β-macrocarpene from (2E,6E)-farnesyl diphosphate proceeds in two steps. The first step is the cyclization to (S)-β-bisabolene. The second step is the isomerization to (S)-β-macrocarpene (cf. EC 5.5.1.17, (S)-β-macrocarpene synthase). The enzyme requires Mg²⁺ or Mn²⁺ for activity.

Links to other databases:

References:

1.	Fujisawa, M., Harada, H., Kenmoku, H., Mizutani, S. and Misawa, N. Cloning and characterization of a novel gene that encodes (S)-β-bisabolene synthase from ginger, Zingiber officinale. Planta 232 (2010) 121–130. [DOI] [PMID: 20229191]

[EC 4.2.3.55 created 2011]

4.2.3.56

Accepted name:

γ-humulene synthase

Reaction:

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

For diagram of humulene-based sequiterpenoid biosynthesis, click here

Other name(s):

humulene cyclase

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (γ-humulene-forming)

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 110639-19-5

References:

1.	Steele, C.L., Crock, J., Bohlmann, J. and Croteau, R. Sesquiterpene synthases from grand fir (Abies grandis). Comparison of constitutive and wound-induced activities, and cDNA isolation, characterization, and bacterial expression of δ-selinene synthase and γ-humulene synthase. J. Biol. Chem. 273 (1998) 2078–2089. [DOI] [PMID: 9442047]
2.	Little, D.B. and Croteau, R.B. Alteration of product formation by directed mutagenesis and truncation of the multiple-product sesquiterpene synthases δ-selinene synthase and γ-humulene synthase. Arch. Biochem. Biophys. 402 (2002) 120–135. [DOI] [PMID: 12051690]

[EC 4.2.3.56 created 2011]

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]

4.2.3.58

Accepted name:

longifolene synthase

Reaction:

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

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

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (longifolene-forming)

Comments:

As well as 61% longifolene the enzyme gives 15% of α-longipinene, 6% longicyclene and traces of other sesquiterpenoids.

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]

[EC 4.2.3.58 created 2011]

4.2.3.59

Accepted name:

(E)-γ-bisabolene synthase

Reaction:

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

For diagram of bisabolene biosynthesis, click here and for diagram of bisabolene biosynthesis, click here

Systematic name:

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

Links to other databases:

References:

1.	Huber, D.P.W., Philippe, R.N., Godard, K.-A., Sturrock, R.N. and Bohlmann, J. Characterization of four terpene synthase cDNAs from methyl jasmonate-induced Douglas-fir, Pseudotsuga menziesii. Phytochemistry 66 (2005) 1427–1439. [DOI] [PMID: 15921711]

[EC 4.2.3.59 created 2011]

4.2.3.60

Accepted name:

germacrene C synthase

Reaction:

(2E,6E)-farnesyl diphosphate = germacrene C + diphosphate

For diagram of germacrene-derived sesquiterpenoid biosynthesis, click here

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (germacrene-C-forming)

Links to other databases:

References:

Colby, S.M., Crock, J., Dowdle-Rizzo, B., Lemaux, P.G. and Croteau, R. Germacrene C synthase from Lycopersicon esculentum cv. VFNT cherry tomato: cDNA isolation, characterization, and bacterial expression of the multiple product sesquiterpene cyclase. Proc. Natl. Acad. Sci. USA 95 (1998) 2216–2221. [DOI] [PMID: 9482865]

[EC 4.2.3.60 created 2011]

4.2.99.21

Accepted name:

isochorismate lyase

Reaction:

isochorismate = salicylate + pyruvate

Other name(s):

salicylate biosynthesis protein pchB; pyochelin biosynthetic protein PchB; isochorismate pyruvate lyase

Systematic name:

isochorismate pyruvate-lyase (salicylate-forming)

Comments:

This enzyme is part of the pathway of salicylate formation from chorismate, and forms an integral part of pathways that produce salicylate-derived siderophores, such as pyochelin and yersiniabactin.

Links to other databases:

References:

1.	Serino, L., Reimmann, C., Baur, H., Beyeler, M., Visca, P. and Haas, D. Structural genes for salicylate biosynthesis from chorismate in Pseudomonas aeruginosa. Mol. Gen. Genet. 249 (1995) 217–228. [PMID: 7500944]
2.	Kerbarh, O., Ciulli, A., Howard, N.I. and Abell, C. Salicylate biosynthesis: overexpression, purification, and characterization of Irp9, a bifunctional salicylate synthase from Yersinia enterocolitica. J. Bacteriol. 187 (2005) 5061–5066. [DOI] [PMID: 16030197]

[EC 4.2.99.21 created 2010]

*EC

4.3.1.16

Accepted name:

threo-3-hydroxy-L-aspartate ammonia-lyase

Reaction:

threo-3-hydroxy-L-aspartate = oxaloacetate + NH₃

Other name(s):

L-threo-3-hydroxyaspartate dehydratase; threo-3-hydroxyaspartate ammonia-lyase

Systematic name:

threo-3-hydroxy-L-aspartate ammonia-lyase (oxaloacetate-forming)

Comments:

A pyridoxal-phosphate protein. The enzyme, purified from the bacterium Pseudomonas sp. T62, is highly specific, and does not accept any other stereoisomer of 3-hydroxyaspartate. Different from EC 4.3.1.20, erythro-3-hydroxy-L-aspartate ammonia-lyase and EC 4.3.1.27, threo-3-hydroxy-D-aspartate ammonia-lyase. Requires a divalent cation such as Mn²⁺, Mg²⁺, or Ca²⁺.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 248270-70-4

References:

Wada, M., Matsumoto, T., Nakamori, S., Sakamoto, M., Kataoka, M., Liu, J.-Q., Itoh, N., Yamada, H. and Shimizu, S. Purification and characterization of a novel enzyme, L-threo-3-hydroxyaspartate dehydratase, from Pseudomonas sp. T62. FEMS Microbiol. Lett. 179 (1999) 147–151. [DOI] [PMID: 10481099]

[EC 4.3.1.16 created 2001, modified 2011]

*EC

4.3.1.20

Accepted name:

erythro-3-hydroxy-L-aspartate ammonia-lyase

Reaction:

erythro-3-hydroxy-L-aspartate = oxaloacetate + NH₃

Other name(s):

erythro-β-hydroxyaspartate dehydratase; erythro-3-hydroxyaspartate dehydratase; erythro-3-hydroxy-L_s-aspartate hydro-lyase (deaminating); erythro-3-hydroxy-L_s-aspartate ammonia-lyase

Systematic name:

erythro-3-hydroxy-L-aspartate ammonia-lyase (oxaloacetate-forming)

Comments:

A pyridoxal-phosphate protein. The enzyme, which was characterized from the bacterium Paracoccus denitrificans NCIMB 8944, is highly specific for the L-isomer of erythro-3-hydroxyaspartate. Different from EC 4.3.1.16, threo-3-hydroxy-L-aspartate ammonia-lyase and EC 4.3.1.27, threo-3-hydroxy-D-aspartate ammonia-lyase. Requires a divalent cation such as Mn²⁺, Mg²⁺, and Ca²⁺.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 37290-74-7

References:

1.	Gibbs, R.G. and Morris, J.G. Purification and properties of erythro-β-hydroxyaspartate dehydratase from Micrococcus denitrificans. Biochem. J. 97 (1965) 547–554. [PMID: 16749162]

[EC 4.3.1.20 created 1972 as EC 4.2.1.38, transferred 2001 to EC 4.3.1.20, modified 2011]

4.3.1.27

Accepted name:

threo-3-hydroxy-D-aspartate ammonia-lyase

Reaction:

threo-3-hydroxy-D-aspartate = oxaloacetate + NH₃

Other name(s):

D-threo-3-hydroxyaspartate dehydratase

Systematic name:

threo-3-hydroxy-D-aspartate ammonia-lyase (oxaloacetate-forming)

Comments:

A pyridoxal-phosphate protein. The enzyme, purified from the bacterium Delftia sp. HT23, also has activity against L-threo-3-hydroxyaspartate, L-erythro-3-hydroxyaspartate, and D-serine. Different from EC 4.3.1.20, erythro-3-hydroxy-L-aspartate ammonia-lyase and EC 4.3.1.16, threo-3-hydroxy-L-aspartate ammonia-lyase. Requires a divalent cation such as Mn²⁺, Co²⁺ or Ni²⁺.

Links to other databases:

References:

1.	Maeda, T., Takeda, Y., Murakami, T., Yokota, A. and Wada, M. Purification, characterization and amino acid sequence of a novel enzyme, D-threo-3-hydroxyaspartate dehydratase, from Delftia sp. HT23. J. Biochem. 148 (2010) 705–712. [DOI] [PMID: 20843822]

[EC 4.3.1.27 created 2011]

*EC

5.4.99.12

Accepted name:

tRNA pseudouridine^38-40 synthase

Reaction:

tRNA uridine^38-40 = tRNA pseudouridine^38-40

Other name(s):

TruA; tRNA pseudouridine synthase I; PSUI; hisT (gene name)

Systematic name:

tRNA-uridine^38-40 uracil mutase

Comments:

The uridylate residues at positions 38, 39 and 40 of nearly all tRNAs are isomerized to pseudouridine. TruA specifically modifies uridines at positions 38, 39, and/or 40 in the anticodon stem loop of tRNAs with highly divergent sequences and structures [1].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 61506-89-6

References:

1.	Hur, S. and Stroud, R.M. How U38, 39, and 40 of many tRNAs become the targets for pseudouridylation by TruA. Mol. Cell 26 (2007) 189–203. [DOI] [PMID: 17466622]
2.	Huang, L., Pookanjanatavip, M., Gu, X. and Santi, D.V. A conserved aspartate of tRNA pseudouridine synthase is essential for activity and a probable nucleophilic catalyst. Biochemistry 37 (1998) 344–351. [DOI] [PMID: 9425056]
3.	Kammen, H.O., Marvel, C.C., Hardy, L. and Penhoet, E.E. Purification, structure, and properties of Escherichia coli tRNA pseudouridine synthase I. J. Biol. Chem. 263 (1988) 2255–2263. [PMID: 3276686]
4.	Turnbough, C.L., Jr., Neill, R.J., Landsberg, R. and Ames, B.N. Pseudouridylation of tRNAs and its role in regulation in Salmonella typhimurium. J. Biol. Chem. 254 (1979) 5111–5119. [PMID: 376505]
5.	Zhao, X. and Horne, D.A. The role of cysteine residues in the rearrangement of uridine to pseudouridine catalyzed by pseudouridine synthase I. J. Biol. Chem. 272 (1997) 1950–1955. [DOI] [PMID: 8999885]
6.	Foster, P.G., Huang, L., Santi, D.V. and Stroud, R.M. The structural basis for tRNA recognition and pseudouridine formation by pseudouridine synthase I. Nat. Struct. Biol. 7 (2000) 23–27. [DOI] [PMID: 10625422]
7.	Dong, X., Bessho, Y., Shibata, R., Nishimoto, M., Shirouzu, M., Kuramitsu, S. and Yokoyama, S. Crystal structure of tRNA pseudouridine synthase TruA from Thermus thermophilus HB8. RNA Biol. 3 (2006) 115–122. [PMID: 17114947]
8.	Arena, F., Ciliberto, G., Ciampi, S. and Cortese, R. Purification of pseudouridylate synthetase I from Salmonella typhimurium. Nucleic Acids Res. 5 (1978) 4523–4536. [DOI] [PMID: 370771]

[EC 5.4.99.12 created 1990, modified 2011]

5.4.99.19

Accepted name:

16S rRNA pseudouridine⁵¹⁶ synthase

Reaction:

16S rRNA uridine⁵¹⁶ = 16S rRNA pseudouridine⁵¹⁶

Other name(s):

16S RNA pseudouridine⁵¹⁶ synthase; 16S PsiI516 synthase; 16S RNA Ψ⁵¹⁶ synthase; RNA pseudouridine synthase RsuA; RsuA; 16S RNA pseudouridine 516 synthase

Systematic name:

16S rRNA-uridine⁵¹⁶ uracil mutase

Comments:

The enzyme is specific for uridine⁵¹⁶ in 16S rRNA. In vitro, the enzyme does not modify free 16S rRNA. The preferred substrate is a 5′-terminal fragment of 16S rRNA complexed with 30S ribosomal proteins [1].

Links to other databases:

References:

1.	Wrzesinski, J., Bakin, A., Nurse, K., Lane, B.G. and Ofengand, J. Purification, cloning, and properties of the 16S RNA pseudouridine 516 synthase from Escherichia coli. Biochemistry 34 (1995) 8904–8913. [PMID: 7612632]
2.	Conrad, J., Niu, L., Rudd, K., Lane, B.G. and Ofengand, J. 16S ribosomal RNA pseudouridine synthase RsuA of Escherichia coli: deletion, mutation of the conserved Asp¹⁰² residue, and sequence comparison among all other pseudouridine synthases. RNA 5 (1999) 751–763. [PMID: 10376875]
3.	Sivaraman, J., Sauve, V., Larocque, R., Stura, E.A., Schrag, J.D., Cygler, M. and Matte, A. Structure of the 16S rRNA pseudouridine synthase RsuA bound to uracil and UMP. Nat. Struct. Biol. 9 (2002) 353–358. [DOI] [PMID: 11953756]

[EC 5.4.99.19 created 2011]

5.4.99.20

Accepted name:

23S rRNA pseudouridine²⁴⁵⁷ synthase

Reaction:

23S rRNA uridine²⁴⁵⁷ = 23S rRNA pseudouridine²⁴⁵⁷

Other name(s):

RluE; YmfC

Systematic name:

23S rRNA-uridine²⁴⁵⁷ uracil mutase

Comments:

The enzyme modifies uridine²⁴⁵⁷ in a stem of 23S RNA in Escherichia coli.

Links to other databases:

References:

1.	Del Campo, M., Kaya, Y. and Ofengand, J. Identification and site of action of the remaining four putative pseudouridine synthases in Escherichia coli. RNA 7 (2001) 1603–1615. [PMID: 11720289]
2.	Pan, H., Ho, J.D., Stroud, R.M. and Finer-Moore, J. The crystal structure of E. coli rRNA pseudouridine synthase RluE. J. Mol. Biol. 367 (2007) 1459–1470. [DOI] [PMID: 17320904]

[EC 5.4.99.20 created 2011]

5.4.99.21

Accepted name:

23S rRNA pseudouridine²⁶⁰⁴ synthase

Reaction:

23S rRNA uridine²⁶⁰⁴ = 23S rRNA pseudouridine²⁶⁰⁴

Other name(s):

RluF; YjbC

Systematic name:

23S rRNA-uridine²⁶⁰⁴ uracil mutase

Comments:

The enzyme is not completely specific for uridine²⁶⁰⁴ and can, to a small extent, also react with uridine²⁶⁰⁵ [1].

Links to other databases:

References:

1.	Del Campo, M., Kaya, Y. and Ofengand, J. Identification and site of action of the remaining four putative pseudouridine synthases in Escherichia coli. RNA 7 (2001) 1603–1615. [PMID: 11720289]
2.	Alian, A., DeGiovanni, A., Griner, S.L., Finer-Moore, J.S. and Stroud, R.M. Crystal structure of an RluF-RNA complex: a base-pair rearrangement is the key to selectivity of RluF for U²⁶⁰⁴ of the ribosome. J. Mol. Biol. 388 (2009) 785–800. [DOI] [PMID: 19298824]
3.	Sunita, S., Zhenxing, H., Swaathi, J., Cygler, M., Matte, A. and Sivaraman, J. Domain organization and crystal structure of the catalytic domain of E. coli RluF, a pseudouridine synthase that acts on 23S rRNA. J. Mol. Biol. 359 (2006) 998–1009. [DOI] [PMID: 16712869]

[EC 5.4.99.21 created 2011]

5.4.99.22

Accepted name:

23S rRNA pseudouridine²⁶⁰⁵ synthase

Reaction:

23S rRNA uridine²⁶⁰⁵ = 23S rRNA pseudouridine²⁶⁰⁵

Other name(s):

RluB; YciL

Systematic name:

23S rRNA-uridine²⁶⁰⁵ uracil mutase

Comments:

Pseudouridine synthase RluB converts uridine²⁶⁰⁵ of 23S rRNA to pseudouridine.

Links to other databases:

References:

1.	Del Campo, M., Kaya, Y. and Ofengand, J. Identification and site of action of the remaining four putative pseudouridine synthases in Escherichia coli. RNA 7 (2001) 1603–1615. [PMID: 11720289]
2.	Jiang, M., Sullivan, S.M., Walker, A.K., Strahler, J.R., Andrews, P.C. and Maddock, J.R. Identification of novel Escherichia coli ribosome-associated proteins using isobaric tags and multidimensional protein identification techniques. J. Bacteriol. 189 (2007) 3434–3444. [DOI] [PMID: 17337586]

[EC 5.4.99.22 created 2011]

5.4.99.23

Accepted name:

23S rRNA pseudouridine^{1911/1915/1917} synthase

Reaction:

23S rRNA uridine¹⁹¹¹/uridine¹⁹¹⁵/uridine¹⁹¹⁷ = 23S rRNA pseudouridine¹⁹¹¹/pseudouridine¹⁹¹⁵/pseudouridine¹⁹¹⁷

Other name(s):

RluD; pseudouridine synthase RluD

Systematic name:

23S rRNA-uridine^{1911/1915/1917} uracil mutase

Comments:

Pseudouridine synthase RluD converts uridines at positions 1911, 1915, and 1917 of 23S rRNA to pseudouridines. These nucleotides are located in the functionally important helix-loop 69 of 23S rRNA [1].

Links to other databases:

References:

1.	Leppik, M., Peil, L., Kipper, K., Liiv, A. and Remme, J. Substrate specificity of the pseudouridine synthase RluD in Escherichia coli. FEBS J. 274 (2007) 5759–5766. [DOI] [PMID: 17937767]
2.	Ejby, M., Sorensen, M.A. and Pedersen, S. Pseudouridylation of helix 69 of 23S rRNA is necessary for an effective translation termination. Proc. Natl. Acad. Sci. USA 104 (2007) 19410–19415. [DOI] [PMID: 18032607]
3.	Sivaraman, J., Iannuzzi, P., Cygler, M. and Matte, A. Crystal structure of the RluD pseudouridine synthase catalytic module, an enzyme that modifies 23S rRNA and is essential for normal cell growth of Escherichia coli. J. Mol. Biol. 335 (2004) 87–101. [DOI] [PMID: 14659742]
4.	Wrzesinski, J., Bakin, A., Ofengand, J. and Lane, B.G. Isolation and properties of Escherichia coli 23S-RNA pseudouridine 1911, 1915, 1917 synthase (RluD). IUBMB Life 50 (2000) 33–37. [DOI] [PMID: 11087118]

[EC 5.4.99.23 created 2011]

5.4.99.24

Accepted name:

23S rRNA pseudouridine^{955/2504/2580} synthase

Reaction:

23S rRNA uridine⁹⁵⁵/uridine²⁵⁰⁴/uridine²⁵⁸⁰ = 23S rRNA pseudouridine⁹⁵⁵/pseudouridine²⁵⁰⁴/pseudouridine²⁵⁸⁰

Other name(s):

RluC; pseudouridine synthase RluC

Systematic name:

23S rRNA-uridine^{955/2504/2580} uracil mutase

Comments:

The enzyme converts uridines at position 955, 2504 and 2580 of 23S rRNA to pseudouridines.

Links to other databases:

References:

1.	Jiang, M., Sullivan, S.M., Walker, A.K., Strahler, J.R., Andrews, P.C. and Maddock, J.R. Identification of novel Escherichia coli ribosome-associated proteins using isobaric tags and multidimensional protein identification techniques. J. Bacteriol. 189 (2007) 3434–3444. [DOI] [PMID: 17337586]
2.	Conrad, J., Sun, D., Englund, N. and Ofengand, J. The rluC gene of Escherichia coli codes for a pseudouridine synthase that is solely responsible for synthesis of pseudouridine at positions 955, 2504, and 2580 in 23 S ribosomal RNA. J. Biol. Chem. 273 (1998) 18562–18566. [DOI] [PMID: 9660827]
3.	Corollo, D., Blair-Johnson, M., Conrad, J., Fiedler, T., Sun, D., Wang, L., Ofengand, J. and Fenna, R. Crystallization and characterization of a fragment of pseudouridine synthase RluC from Escherichia coli. Acta Crystallogr. D Biol. Crystallogr. 55 (1999) 302–304. [DOI] [PMID: 10089432]
4.	Toh, S.M. and Mankin, A.S. An indigenous posttranscriptional modification in the ribosomal peptidyl transferase center confers resistance to an array of protein synthesis inhibitors. J. Mol. Biol. 380 (2008) 593–597. [DOI] [PMID: 18554609]

[EC 5.4.99.24 created 2011]

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]

5.4.99.26

Accepted name:

tRNA pseudouridine⁶⁵ synthase

Reaction:

tRNA uridine⁶⁵ = tRNA pseudouridine⁶⁵

Other name(s):

TruC; YqcB

Systematic name:

tRNA-uridine⁶⁵ uracil mutase

Comments:

TruC specifically modifies uridines at positions 65 in tRNA.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 430429-15-5

References:

1.	Del Campo, M., Kaya, Y. and Ofengand, J. Identification and site of action of the remaining four putative pseudouridine synthases in Escherichia coli. RNA 7 (2001) 1603–1615. [PMID: 11720289]

[EC 5.4.99.26 created 2011]

5.4.99.27

Accepted name:

tRNA pseudouridine¹³ synthase

Reaction:

tRNA uridine¹³ = tRNA pseudouridine¹³

Other name(s):

TruD; YgbO; tRNA PSI13 synthase; RNA:PSI-synthase Pus7p; Pus7p; RNA:pseudouridine-synthase Pus7p; Pus7 protein

Systematic name:

tRNA-uridine¹³ uracil mutase

Comments:

Pseudouridine synthase TruD from Escherichia coli specifically acts on uridine¹³ in tRNA [2,3]. The Pus7 protein from Saccharomyces cerevisiae is a multisite-multisubstrate pseudouridine synthase that is able to modify uridine¹³ in several yeast tRNAs, uridine³⁵ in the pre-tRNA^Tyr, uridine³⁵ in U2 small nuclear RNA, and uridine⁵⁰ in 5S rRNA [5].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 430429-15-5

References:

1.	Ericsson, U.B., Nordlund, P. and Hallberg, B.M. X-ray structure of tRNA pseudouridine synthase TruD reveals an inserted domain with a novel fold. FEBS Lett. 565 (2004) 59–64. [DOI] [PMID: 15135053]
2.	Chan, C.M. and Huang, R.H. Enzymatic characterization and mutational studies of TruD—the fifth family of pseudouridine synthases. Arch. Biochem. Biophys. 489 (2009) 15–19. [DOI] [PMID: 19664587]
3.	Kaya, Y. and Ofengand, J. A novel unanticipated type of pseudouridine synthase with homologs in bacteria, archaea, and eukarya. RNA 9 (2003) 711–721. [DOI] [PMID: 12756329]
4.	Behm-Ansmant, I., Urban, A., Ma, X., Yu, Y.T., Motorin, Y. and Branlant, C. The Saccharomyces cerevisiae U2 snRNA:pseudouridine-synthase Pus7p is a novel multisite-multisubstrate RNA:Ψ-synthase also acting on tRNAs. RNA 9 (2003) 1371–1382. [DOI] [PMID: 14561887]
5.	Urban, A., Behm-Ansmant, I., Branlant, C. and Motorin, Y. RNA sequence and two-dimensional structure features required for efficient substrate modification by the Saccharomyces cerevisiae RNA:Ψ-synthase Pus7p. J. Biol. Chem. 284 (2009) 5845–5858. [DOI] [PMID: 19114708]

[EC 5.4.99.27 created 2011]

5.4.99.28

Accepted name:

tRNA pseudouridine³² synthase

Reaction:

tRNA uridine³² = tRNA pseudouridine³²

Other name(s):

RluA (ambiguous); pseudouridine synthase RluA (ambiguous); Pus9p; Rib₂/Pus8p

Systematic name:

tRNA-uridine³² uracil mutase

Comments:

The dual-specificity enzyme from Escherichia coli also catalyses the formation of pseudouridine⁷⁴⁶ in 23S rRNA [5]. cf. EC 5.4.99.29 (23S rRNA pseudouridine⁷⁴⁶ synthase).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 430429-15-5

References:

1.	Hoang, C., Chen, J., Vizthum, C.A., Kandel, J.M., Hamilton, C.S., Mueller, E.G. and Ferre-D'Amare, A.R. Crystal structure of pseudouridine synthase RluA: indirect sequence readout through protein-induced RNA structure. Mol. Cell 24 (2006) 535–545. [DOI] [PMID: 17188032]
2.	Spedaliere, C.J., Hamilton, C.S. and Mueller, E.G. Functional importance of motif I of pseudouridine synthases: mutagenesis of aligned lysine and proline residues. Biochemistry 39 (2000) 9459–9465. [DOI] [PMID: 10924141]
3.	Raychaudhuri, S., Niu, L., Conrad, J., Lane, B.G. and Ofengand, J. Functional effect of deletion and mutation of the Escherichia coli ribosomal RNA and tRNA pseudouridine synthase RluA. J. Biol. Chem. 274 (1999) 18880–18886. [DOI] [PMID: 10383384]
4.	Ramamurthy, V., Swann, S.L., Spedaliere, C.J. and Mueller, E.G. Role of cysteine residues in pseudouridine synthases of different families. Biochemistry 38 (1999) 13106–13111. [DOI] [PMID: 10529181]
5.	Wrzesinski, J., Nurse, K., Bakin, A., Lane, B.G. and Ofengand, J. A dual-specificity pseudouridine synthase: an Escherichia coli synthase purified and cloned on the basis of its specificity for Ψ⁷⁴⁶ in 23S RNA is also specific for Ψ³² in tRNA^Phe. RNA 1 (1995) 437–448. [PMID: 7493321]
6.	Behm-Ansmant, I., Grosjean, H., Massenet, S., Motorin, Y. and Branlant, C. Pseudouridylation at position 32 of mitochondrial and cytoplasmic tRNAs requires two distinct enzymes in Saccharomyces cerevisiae. J. Biol. Chem. 279 (2004) 52998–53006. [DOI] [PMID: 15466869]

[EC 5.4.99.28 created 2011, modified 2011]

5.4.99.29

Accepted name:

23S rRNA pseudouridine⁷⁴⁶ synthase

Reaction:

23S rRNA uridine⁷⁴⁶ = 23S rRNA pseudouridine⁷⁴⁶

Other name(s):

RluA (ambiguous); 23S RNA PSI746 synthase; 23S rRNA pseudouridine synthase; pseudouridine synthase RluA (ambiguous)

Systematic name:

23S rRNA-uridine⁷⁴⁶ uracil mutase

Comments:

RluA is the sole protein responsible for the in vivo formation of 23S RNA pseudouridine⁷⁴⁶ [2]. The dual-specificity enzyme also catalyses the formation of uridine³² in tRNA [3]. cf. EC 5.4.99.28 (tRNA pseudouridine³² synthase).

Links to other databases:

References:

1.	Hoang, C., Chen, J., Vizthum, C.A., Kandel, J.M., Hamilton, C.S., Mueller, E.G. and Ferre-D'Amare, A.R. Crystal structure of pseudouridine synthase RluA: indirect sequence readout through protein-induced RNA structure. Mol. Cell 24 (2006) 535–545. [DOI] [PMID: 17188032]
2.	Raychaudhuri, S., Niu, L., Conrad, J., Lane, B.G. and Ofengand, J. Functional effect of deletion and mutation of the Escherichia coli ribosomal RNA and tRNA pseudouridine synthase RluA. J. Biol. Chem. 274 (1999) 18880–18886. [DOI] [PMID: 10383384]
3.	Wrzesinski, J., Nurse, K., Bakin, A., Lane, B.G. and Ofengand, J. A dual-specificity pseudouridine synthase: an Escherichia coli synthase purified and cloned on the basis of its specificity for Ψ⁷⁴⁶ in 23S RNA is also specific for Ψ³² in tRNA^Phe. RNA 1 (1995) 437–448. [PMID: 7493321]

[EC 5.4.99.29 created 2011]

5.4.99.30

Accepted name:

UDP-arabinopyranose mutase

Reaction:

UDP-β-L-arabinofuranose = UDP-β-L-arabinopyranose

Other name(s):

Os03g40270 protein; UAM1; UAM3; RGP1; RGP3; OsUAM1; OsUAM2; Os03g0599800 protein; Os07g41360 protein

Systematic name:

UDP-arabinopyranose pyranomutase

Comments:

The reaction is reversible and at thermodynamic equilibrium the pyranose form is favored over the furanose form (90:10) [1].

Links to other databases:

References:

1.	Konishi, T., Takeda, T., Miyazaki, Y., Ohnishi-Kameyama, M., Hayashi, T., O'Neill, M.A. and Ishii, T. A plant mutase that interconverts UDP-arabinofuranose and UDP-arabinopyranose. Glycobiology 17 (2007) 345–354. [DOI] [PMID: 17182701]
2.	Konishi, T., Ohnishi-Kameyama, M., Funane, K., Miyazaki, Y., Konishi, T. and Ishii, T. An arginyl residue in rice UDP-arabinopyranose mutase is required for catalytic activity and autoglycosylation. Carbohydr. Res. 345 (2010) 787–791. [DOI] [PMID: 20149347]
3.	Konishi, T., Miyazaki, Y., Yamakawa, S., Iwai, H., Satoh, S. and Ishii, T. Purification and biochemical characterization of recombinant rice UDP-arabinopyranose mutase generated in insect cells. Biosci. Biotechnol. Biochem. 74 (2010) 191–194. [DOI] [PMID: 20057139]

[EC 5.4.99.30 created 2011]

5.5.1.17

Accepted name:

(S)-β-macrocarpene synthase

Reaction:

(S)-β-bisabolene = (S)-β-macrocarpene

For diagram of biosynthesis of bicyclic sesquiterpenoids derived from bisabolyl cation, click here and for diagram of bisabolene and macrocarpene biosynthesis, click here

Other name(s):

TPS6; TPS11; (S)-β-macrocarpene lyase (decyclizing)

Systematic name:

(S)-β-macrocarpene lyase (ring-opening)

Comments:

The synthesis of (S)-β-macrocarpene from (2E,6E)-farnesyl diphosphate proceeds in two steps. The first step is the cyclization to (S)-β-bisabolene (cf. EC 4.2.3.55, (S)-β-bisabolene synthase). The second step is the isomerization to (S)-β-macrocarpene.

Links to other databases:

References:

Kollner, T.G., Schnee, C., Li, S., Svatos, A., Schneider, B., Gershenzon, J. and Degenhardt, J. Protonation of a neutral (S)-β-bisabolene intermediate is involved in (S)-β-macrocarpene formation by the maize sesquiterpene synthases TPS6 and TPS11. J. Biol. Chem. 283 (2008) 20779–20788. [DOI] [PMID: 18524777]

[EC 5.5.1.17 created 2011]

6.3.2.36

Accepted name:

4-phosphopantoate—β-alanine ligase

Reaction:

ATP + (R)-4-phosphopantoate + β-alanine = AMP + diphosphate + (R)-4′-phosphopantothenate

Other name(s):

phosphopantothenate synthetase; TK1686 protein

Systematic name:

(R)-4-phosphopantoate:β-alanine ligase (AMP-forming)

Comments:

The conversion of (R)-pantoate to (R)-4′-phosphopantothenate is part of the pathway leading to biosynthesis of 4′-phosphopantetheine, an essential cofactor of coenzyme A and acyl-carrier protein. In bacteria and eukaryotes this conversion is performed by condensation with β-alanine, followed by phosphorylation (EC 6.3.2.1 [pantoate—β-alanine ligase] and EC 2.7.1.33 [pantothenate kinase], respectively). In archaea the order of these two steps is reversed, and phosphorylation precedes condensation with β-alanine. The two archaeal enzymes that catalyse this conversion are EC 2.7.1.169, pantoate kinase, and this enzyme.

Links to other databases: