Proposed Changes to the Enzyme List

References:

1.	Shanati, T., Lockie, C., Beloti, L., Grogan, G. and Ansorge-Schumacher, M.B. Two enantiocomplementary ephedrine dehydrogenases from Arthrobacter sp. TS-15 with broad substrate specificity. ACS Catal. 9 (2019) 6202–6211.
2.	Shanati, T., Ansorge-Schumacher, M. Enzymes and methods for the stereoselective reduction of carbonyl compounds, oxidation and stereoselective reductive amination - for the enantioselective preparation of alcohol amine compounds. (2019) Patent WO2019002459.

[EC 1.1.1.423 created 2020, modified 2020]

1.1.1.424

Accepted name:

D-xylose 1-dehydrogenase (NADP⁺, D-xylono-1,4-lactone-forming)

Reaction:

D-xylose + NADP⁺ = D-xylono-1,4-lactone + NADPH + H⁺

Other name(s):

xacA (gene name); xdh (gene name)

Systematic name:

D-xylose:NADP⁺ 1-oxidoreductase (D-xylono-1,4-lactone-forming)

Comments:

The enzyme, which participates in the degradation of D-xylose, has been characterized from several halophilic archaeal species. cf. EC 1.1.1.179, D-xylose 1-dehydrogenase (NADP⁺, D-xylono-1,5-lactone-forming).

Links to other databases:

References:

1.	Johnsen, U. and Schonheit, P. Novel xylose dehydrogenase in the halophilic archaeon Haloarcula marismortui. J. Bacteriol. 186 (2004) 6198–6207. [PMID: 15342590]
2.	Johnsen, U., Dambeck, M., Zaiss, H., Fuhrer, T., Soppa, J., Sauer, U. and Schonheit, P. D-Xylose degradation pathway in the halophilic archaeon Haloferax volcanii. J. Biol. Chem. 284 (2009) 27290–27303. [DOI] [PMID: 19584053]
3.	Sutter, J.M., Johnsen, U. and Schonheit, P. Characterization of a pentonolactonase involved in D-xylose and L-arabinose catabolism in the haloarchaeon Haloferax volcanii. FEMS Microbiol. Lett. 364 (2017) . [PMID: 28854683]

[EC 1.1.1.424 created 2020]

1.1 Acting on the CH-OH group of donors

1.1.7 With an iron-sulfur protein as acceptor

1.1.7.1

Accepted name:

4-hydroxybenzoyl-CoA reductase

Reaction:

benzoyl-CoA + oxidized ferredoxin + H₂O = 4-hydroxybenzoyl-CoA + reduced ferredoxin

Other name(s):

4-hydroxybenzoyl-CoA reductase (dehydroxylating); 4-hydroxybenzoyl-CoA:(acceptor) oxidoreductase; benzoyl-CoA:acceptor oxidoreductase

Systematic name:

benzoyl-CoA:oxidized ferredoxin oxidoreductase

Comments:

A molybdenum-flavin-iron-sulfur protein that is involved in the anaerobic pathway of phenol metabolism in bacteria. A ferredoxin with two [4Fe-4S] clusters functions as the natural electron donor [3].

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 133758-58-4

References:

1.	Glockler, R., Tschech, A. and Fuchs, G. Reductive dehydroxylation of 4-hydroxybenzoyl-CoA to benzoyl-CoA in a denitrifying, phenol-degrading Pseudomonas species. FEBS Lett. 251 (1989) 237–240. [DOI] [PMID: 2753161]
2.	Heider, J., Boll, M., Breese, K., Breinig, S., Ebenau-Jehle, C., Feil, U., Gad'on, N., Laempe, D., Leuthner, B., Mohamed, M.E., Schneider, S., Burchhardt, G. and Fuchs, G. Differential induction of enzymes involved in anaerobic metabolism of aromatic compounds in the denitrifying bacterium Thauera aromatica. Arch. Microbiol. 170 (1998) 120–131. [DOI] [PMID: 9683649]
3.	Breese, K. and Fuchs, G. 4-Hydroxybenzoyl-CoA reductase (dehydroxylating) from the denitrifying bacterium Thauera aromatica - prosthetic groups, electron donor, and genes of a member of the molybdenum-flavin-iron-sulfur proteins. Eur. J. Biochem. 251 (1998) 916–923. [DOI] [PMID: 9490068]
4.	Brackmann, R. and Fuchs, G. Enzymes of anaerobic metabolism of phenolic compounds. 4-Hydroxybenzoyl-CoA reductase (dehydroxylating) from a denitrifying Pseudomonas species. Eur. J. Biochem. 213 (1993) 563–571. [DOI] [PMID: 8477729]
5.	Heider, J. and Fuchs, G. Anaerobic metabolism of aromatic compounds. Eur. J. Biochem. 243 (1997) 577–596. [DOI] [PMID: 9057820]

[EC 1.1.7.1 created 2000 as EC 1.3.99.20, transferred 2011 to EC 1.3.7.9, transferred 2020 to EC 1.1.7.1]

1.2.2.4

Deleted entry:

carbon-monoxide dehydrogenase (cytochrome b-561). Now classified as EC 1.2.5.3, aerobic carbon monoxide dehydrogenase

[EC 1.2.2.4 created 1999 (EC 1.2.3.10 created 1990, incorporated 2003), modified 2003, deleted 2020]

*EC

1.3.1.34

Accepted name:

2,4-dienoyl-CoA reductase [(2E)-enoyl-CoA-producing]

Reaction:

(1) a (2E)-2-enoyl-CoA + NADP⁺ = a (2E,4E)-2,4-dienoyl-CoA + NADPH + H⁺
(2) a (2E)-2-enoyl-CoA + NADP⁺ = a (2E,4Z)-2,4-dienoyl-CoA + NADPH + H⁺

Other name(s):

fadH (gene name); 4-enoyl-CoA reductase (NADPH) (ambiguous); 4-enoyl coenzyme A (reduced nicotinamide adenine dinucleotide phosphate) reductase (ambiguous); 4-enoyl-CoA reductase (ambiguous); 2,4-dienoyl-CoA reductase (NADPH) (ambiguous); trans-2,3-didehydroacyl-CoA:NADP⁺ 4-oxidoreductase

Systematic name:

(2E)-2-enoyl-CoA:NADP⁺ 4-oxidoreductase

Comments:

This bacterial enzyme catalyses the reduction of either (2E,4E)-2,4-dienoyl-CoA or (2E,4Z)-2,4-dienoyl-CoA to (2E)-2-enoyl-CoA. The enzyme from Escherichia coli contains FAD, FMN, and an [4Fe-4S] iron sulfur cluster. cf. EC 1.3.1.124, 2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 82869-38-3

References:

1.	Dommes, V., Luster, W., Cvetanovic, M. and Kunau, W.-H. Purification by affinity chromatography of 2,4-dienoyl-CoA reductases from bovine liver and Escherichia coli. Eur. J. Biochem. 125 (1982) 335–341. [DOI] [PMID: 6749495]
2.	Dommes, V. and Kunau, W.H. 2,4-Dienoyl coenzyme A reductases from bovine liver and Escherichia coli. Comparison of properties. J. Biol. Chem. 259 (1984) 1781–1788. [PMID: 6363415]
3.	You, S.Y., Cosloy, S. and Schulz, H. Evidence for the essential function of 2,4-dienoyl-coenzyme A reductase in the β-oxidation of unsaturated fatty acids in vivo. Isolation and characterization of an Escherichia coli mutant with a defective 2,4-dienoyl-coenzyme A reductase. J. Biol. Chem. 264 (1989) 16489–16495. [PMID: 2506179]
4.	He, X.Y., Yang, S.Y. and Schulz, H. Cloning and expression of the fadH gene and characterization of the gene product 2,4-dienoyl coenzyme A reductase from Escherichia coli. Eur. J. Biochem. 248 (1997) 516–520. [PMID: 9346310]
5.	Liang, X., Thorpe, C. and Schulz, H. 2,4-Dienoyl-CoA reductase from Escherichia coli is a novel iron-sulfur flavoprotein that functions in fatty acid β-oxidation. Arch. Biochem. Biophys. 380 (2000) 373–379. [PMID: 10933894]
6.	Hubbard, P.A., Liang, X., Schulz, H. and Kim, J.J. The crystal structure and reaction mechanism of Escherichia coli 2,4-dienoyl-CoA reductase. J. Biol. Chem. 278 (2003) 37553–37560. [PMID: 12840019]
7.	Tu, X., Hubbard, P.A., Kim, J.J. and Schulz, H. Two distinct proton donors at the active site of Escherichia coli 2,4-dienoyl-CoA reductase are responsible for the formation of different products. Biochemistry 47 (2008) 1167–1175. [PMID: 18171025]

[EC 1.3.1.34 created 1984, modified 1986, modified 2020]

1.3.1.124

Accepted name:

2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing]

Reaction:

(1) a (3E)-3-enoyl-CoA + NADP⁺ = a (2E,4E)-2,4-dienoyl-CoA + NADPH + H⁺
(2) a (3E)-3-enoyl-CoA + NADP⁺ = a (2E,4Z)-2,4-dienoyl-CoA + NADPH + H⁺

Other name(s):

SPS19 (gene name); DECR1 (gene name); DECR2 (gene name); Δ²,Δ⁴-dienoyl-CoA reductase (ambiguous)

Systematic name:

(3E)-3-enoyl-CoA:NADP⁺ 4-oxidoreductase

Comments:

This enzyme, characterized from eukaryotic organisms, catalyses the reduction of either (2E,4E)-2,4-dienoyl-CoA or (2E,4Z)-2,4-dienoyl-CoA to (3E)-3-enoyl-CoA. The best substrates for the enzyme from bovine liver have a chain-length of 8 or 10 carbons. Mammals possess both mitochondrial and peroxisomal variants of this enzyme. cf. EC 1.3.1.34, 2,4-dienoyl-CoA reductase [(2E)-enoyl-CoA-producing].

Links to other databases:

References:

1.	Kunau, W.-H. and Dommes, P. Degradation of unsaturated fatty acids. Identification of intermediates in the degradation of cis-4-decenoly-CoA by extracts of beef-liver mitochondria. Eur. J. Biochem. 91 (1978) 533–544. [DOI] [PMID: 729581]
2.	Dommes, V., Luster, W., Cvetanovic, M. and Kunau, W.-H. Purification by affinity chromatography of 2,4-dienoyl-CoA reductases from bovine liver and Escherichia coli. Eur. J. Biochem. 125 (1982) 335–341. [DOI] [PMID: 6749495]
3.	Gurvitz, A., Rottensteiner, H., Kilpelainen, S.H., Hartig, A., Hiltunen, J.K., Binder, M., Dawes, I.W. and Hamilton, B. The Saccharomyces cerevisiae peroxisomal 2,4-dienoyl-CoA reductase is encoded by the oleate-inducible gene SPS19. J. Biol. Chem. 272 (1997) 22140–22147. [PMID: 9268358]
4.	Geisbrecht, B.V., Liang, X., Morrell, J.C., Schulz, H. and Gould, S.J. The mouse gene PDCR encodes a peroxisomal δ², δ⁴-dienoyl-CoA reductase. J. Biol. Chem. 274 (1999) 25814–25820. [PMID: 10464321]
5.	De Nys, K., Meyhi, E., Mannaerts, G.P., Fransen, M. and Van Veldhoven, P.P. Characterisation of human peroxisomal 2,4-dienoyl-CoA reductase. Biochim. Biophys. Acta 1533 (2001) 66–72. [PMID: 11514237]
6.	Alphey, M.S., Yu, W., Byres, E., Li, D. and Hunter, W.N. Structure and reactivity of human mitochondrial 2,4-dienoyl-CoA reductase: enzyme-ligand interactions in a distinctive short-chain reductase active site. J. Biol. Chem. 280 (2005) 3068–3077. [PMID: 15531764]

[EC 1.3.1.124 created 2020]

1.3.3.16

Accepted name:

oxazoline dehydrogenase

Reaction:

(1) a [protein]-(1S,4R)-2-(C-substituted-aminomethyl)-4-acyl-2-thiazoline + O₂ = a [protein]-(S)-2-(C-substituted-aminomethyl)-4-acyl-1,3-thiazole + H₂O₂
(2) a [protein]-(S,S)-2-(C-substituted-aminomethyl)-4-acyl-2-oxazoline + O₂ = a [protein]-(S)-2-(C-substituted-aminomethyl)-4-acyl-1,3-oxazole + H₂O₂
(3) a [protein]-(S,S)-2-(C-substituted-aminomethyl)-4-acyl-5-methyl-2-oxazoline + O₂ = a [protein]-(S)-2-(C-substituted-aminomethyl)-4-acyl-5-methyl-1,3-oxazole + H₂O₂

Other name(s):

azoline oxidase; thiazoline oxidase; cyanobactin oxidase; patG (gene name); mcaG (gene name); artG (gene name); lynG (gene name); tenG (gene name)

Systematic name:

a [protein]-2-oxazoline:oxygen oxidoreductase (2-oxazole-forming)

Comments:

Contains FMN. This enzyme oxidizes 2-oxazoline, 5-methyl-2-oxazoline, and 2-thiazoline within peptides, which were formed by EC 6.2.2.2, oxazoline synthase, and EC 6.2.2.3, thiazoline synthase, to the respective pyrrole-type rings. The enzyme is found as either a stand-alone protein or as a domain within a multifunctional protein (the G protein) that also functions as a peptidase.

Links to other databases:

References:

1.	Li, Y.M., Milne, J.C., Madison, L.L., Kolter, R. and Walsh, C.T. From peptide precursors to oxazole and thiazole-containing peptide antibiotics: microcin B17 synthase. Science 274 (1996) 1188–1193. [PMID: 8895467]
2.	Schmidt, E.W., Nelson, J.T., Rasko, D.A., Sudek, S., Eisen, J.A., Haygood, M.G. and Ravel, J. Patellamide A and C biosynthesis by a microcin-like pathway in Prochloron didemni, the cyanobacterial symbiont of Lissoclinum patella. Proc. Natl. Acad. Sci. USA 102 (2005) 7315–7320. [PMID: 15883371]
3.	Bent, A.F., Mann, G., Houssen, W.E., Mykhaylyk, V., Duman, R., Thomas, L., Jaspars, M., Wagner, A. and Naismith, J.H. Structure of the cyanobactin oxidase ThcOx from Cyanothece sp. PCC 7425, the first structure to be solved at Diamond Light Source beamline I23 by means of S-SAD. Acta Crystallogr D Struct Biol 72 (2016) 1174–1180. [PMID: 27841750]
4.	Ghilarov, D., Stevenson, C.EM., Travin, D.Y., Piskunova, J., Serebryakova, M., Maxwell, A., Lawson, D.M. and Severinov, K. Architecture of microcin B17 synthetase: an octameric protein complex converting a ribosomally synthesized peptide into a DNA gyrase poison. Mol. Cell 73 (2019) 749–762.e5. [PMID: 30661981]

[EC 1.3.3.16 created 2020]

*EC

1.3.5.3

Accepted name:

protoporphyrinogen IX dehydrogenase (quinone)

Reaction:

protoporphyrinogen IX + 3 quinone = protoporphyrin IX + 3 quinol

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

Other name(s):

HemG; protoporphyrinogen IX dehydrogenase (menaquinone)

Systematic name:

protoporphyrinogen IX:quinone oxidoreductase

Comments:

Contains FMN. The enzyme participates in heme b biosynthesis. In the bacterium Escherichia coli it interacts with either ubiquinone or menaquinone, depending on whether the organism grows aerobically or anaerobically.

Links to other databases:

References:

1.	Boynton, T.O., Daugherty, L.E., Dailey, T.A. and Dailey, H.A. Identification of Escherichia coli HemG as a novel, menadione-dependent flavodoxin with protoporphyrinogen oxidase activity. Biochemistry 48 (2009) 6705–6711. [DOI] [PMID: 19583219]
2.	Möbius, K., Arias-Cartin, R., Breckau, D., Hännig, A.L., Riedmann, K., Biedendieck, R., Schroder, S., Becher, D., Magalon, A., Moser, J., Jahn, M. and Jahn, D. Heme biosynthesis is coupled to electron transport chains for energy generation. Proc. Natl. Acad. Sci. USA 107 (2010) 10436–10441. [PMID: 20484676]

[EC 1.3.5.3 created 2010, modified 2020]

1.3.7.9

Transferred entry:

4-hydroxybenzoyl-CoA reductase. Now classified as EC 1.1.7.1, 4-hydroxybenzoyl-CoA reductase.

[EC 1.3.7.9 created 2000 as EC 1.3.99.20, transferred 2011 to EC 1.3.7.9, deleted 2020]

1.6.99.3

Deleted entry:

NADH dehydrogenase. The activity is covered by EC 7.1.1.2, NADH:ubiquinone reductase (H⁺-translocating)

[EC 1.6.99.3 created 1961 as EC 1.6.2.1, transferred 1965 to EC 1.6.99.3, modified 2018, deleted 2020]

1.8.2.7

Accepted name:

thiocyanate desulfurase

Reaction:

thiocyanate + 2 ferricytochrome c + H₂O = cyanate + sulfur + 2 ferrocytochrome c + 2 H⁺

Other name(s):

TcDH; thiocyanate dehydrogenase

Systematic name:

thiocyanate:cytochrome c oxidoreductase (cyanate and sulfur-forming)

Comments:

The enzyme, characterized from the haloalkaliphilic sulfur-oxidizing bacterium Thioalkalivibrio paradoxus, contains three copper ions in its active site. It catalyses the direct conversion of thiocyanate into cyanate and elemental sulfur without involvement of molecular oxygen.

Links to other databases:

References:

1.	Tikhonova, T.V., Sorokin, D.Y., Hagen, W.R., Khrenova, M.G., Muyzer, G., Rakitina, T.V., Shabalin, I.G., Trofimov, A.A., Tsallagov, S.I. and Popov, V.O. Trinuclear copper biocatalytic center forms an active site of thiocyanate dehydrogenase. Proc. Natl. Acad. Sci. USA (2020) . [PMID: 32094184]

[EC 1.8.2.7 created 2020]

1.11.2.6

Accepted name:

L-tyrosine peroxygenase

Reaction:

L-tyrosine + H₂O₂ = L-dopa + H₂O

Systematic name:

L-tyrosine:hydrogen-peroxide oxidoreductase (L-dopa-forming)

Comments:

The enzyme from the bacterium Streptomyces lincolnensis participates in the biosynthesis of the antibiotic lincomycin A, while that from Streptomyces refuineus is involved in anthramycin biosynthesis. The enzyme, which contains a heme b cofactor, is rapidly inactivated in the presence of hydrogen peroxide, but the presence of L-tyrosine protects it. cf. EC 1.11.2.5, 3-methyl-L-tyrosine peroxygenase.

Links to other databases:

References:

1.	Neusser, D., Schmidt, H., Spizek, J., Novotna, J., Peschke, U., Kaschabeck, S., Tichy, P. and Piepersberg, W. The genes lmbB1 and lmbB2 of Streptomyces lincolnensis encode enzymes involved in the conversion of L-tyrosine to propylproline during the biosynthesis of the antibiotic lincomycin A. Arch. Microbiol. 169 (1998) 322–332. [PMID: 9531633]
2.	Connor, K.L., Colabroy, K.L. and Gerratana, B. A heme peroxidase with a functional role as an L-tyrosine hydroxylase in the biosynthesis of anthramycin. Biochemistry 50 (2011) 8926–8936. [PMID: 21919439]

[EC 1.11.2.6 created 2020]

1.13.11.90

Accepted name:

[1-hydroxy-2-(trimethylamino)ethyl]phosphonate dioxygenase (glycine-betaine-forming)

Reaction:

[(1R)-1-hydroxy-2-(trimethylamino)ethyl]phosphonate + O₂ = glycine betaine + phosphate

Other name(s):

tmpB (gene name)

Systematic name:

[(1R)-1-hydroxy-2-(trimethylamino)ethyl]phosphonate:oxygen 1R-oxidoreductase (glycine-betaine-forming)

Comments:

Requires Fe²⁺. This bacterial enzyme is involved in a degradation pathway for [2-(trimethylamino)ethyl]phosphonate.

Links to other databases:

References:

1.	Rajakovich, L.J., Pandelia, M.E., Mitchell, A.J., Chang, W.C., Zhang, B., Boal, A.K., Krebs, C. and Bollinger, J.M., Jr. A new microbial pathway for organophosphonate degradation catalyzed by two previously misannotated non-heme-iron oxygenases. Biochemistry 58 (2019) 1627–1647. [PMID: 30789718]

[EC 1.13.11.90 created 2020]

1.14.11.72

Accepted name:

[2-(trimethylamino)ethyl]phosphonate dioxygenase

Reaction:

[2-(trimethylamino)ethyl]phosphonate + 2-oxoglutarate + O₂ = [(1R)-1-hydroxy-2-(trimethylamino)ethyl]phosphonate + succinate + CO₂

Other name(s):

tmpA (gene name)

Systematic name:

[2-(trimethylamino)ethyl]phosphonate,2-oxoglutarate:oxygen oxidoreductase (1R-hydroxylating)

Comments:

Requires Fe²⁺ and ascorbate. The enzyme, found in bacteria, participates in a degradation pathway for [2-(trimethylamino)ethyl]phosphonate.

Links to other databases:

References:

1.	Rajakovich, L.J., Pandelia, M.E., Mitchell, A.J., Chang, W.C., Zhang, B., Boal, A.K., Krebs, C. and Bollinger, J.M., Jr. A new microbial pathway for organophosphonate degradation catalyzed by two previously misannotated non-heme-iron oxygenases. Biochemistry 58 (2019) 1627–1647. [PMID: 30789718]

[EC 1.14.11.72 created 2020]

1.14.11.73

Accepted name:

[protein]-arginine 3-hydroxylase

Reaction:

[protein]-L-arginine + 2-oxoglutarate + O₂ = [protein]-(3R)-3-hydroxy-L-arginine + succinate + CO₂

Other name(s):

JMJD5 (gene name)

Systematic name:

[protein]-L-arginine,2-oxoglutarate:oxygen oxidoreductase (3R-hydroxylating)

Comments:

The enzyme, characterized from humans, catalyses the stereoselective formation of the (2S,3R)-hydroxy-L-arginine stereoisomer. So far the enzyme has been shown to act on two substrates - the 40S ribosomal protein S6 (RPS6), which is hydroxylated at R137, and, at a lower activity, RCCD1, a protein involved in chromatin stability, which is hydroxylated at R141. Even though the same stereoisomer is produced by the bacterial EC 1.14.11.47, [50S ribosomal protein L16]-arginine 3-hydroxylase, the two enzymes do not exhibit any cross-reactivity on their respective ribosomal protein substrates.

Links to other databases:

References:

1.	Wilkins, S.E., Islam, M.S., Gannon, J.M., Markolovic, S., Hopkinson, R.J., Ge, W., Schofield, C.J. and Chowdhury, R. JMJD5 is a human arginyl C-3 hydroxylase. Nat. Commun. 9:1180 (2018). [PMID: 29563586]

[EC 1.14.11.73 created 2020]

1.14.11.74

Accepted name:

L-isoleucine 3¹-dioxygenase

Reaction:

L-isoleucine + 2-oxoglutarate + O₂ = 3¹-hydroxy-L-isoleucine + succinate + CO₂

Other name(s):

hilA (gene name); L-isoleucine 4′-dioxygenase (incorrect)

Systematic name:

L-isoleucine,2-oxoglutarate:oxygen oxidoreductase (3¹-hydroxylating)

Comments:

Requires Fe²⁺ and ascorbate. The enzyme has been characterized from the bacterium Pantoea ananatis.

Links to other databases:

References:

Smirnov, S.V., Sokolov, P.M., Kotlyarova, V.A., Samsonova, N.N., Kodera, T., Sugiyama, M., Torii, T., Hibi, M., Shimizu, S., Yokozeki, K. and Ogawa, J. A novel L-isoleucine-4′-dioxygenase and L-isoleucine dihydroxylation cascade in Pantoea ananatis. MicrobiologyOpen 2 (2013) 471–481. [PMID: 23554367]

[EC 1.14.11.74 created 2020]

1.14.11.75

Accepted name:

3¹-hydroxy-L-isoleucine 4-dioxygenase

Reaction:

3¹-hydroxy-L-isoleucine + 2-oxoglutarate + O₂ = (4S)-3¹,4-dihydroxy-L-isoleucine + succinate + CO₂

Other name(s):

hilB (gene name); 4′-hydroxy-L-isoleucine 4-dioxygenase (incorrect)

Systematic name:

3¹-hydroxy-L-isoleucine,2-oxoglutarate:oxygen oxidoreductase (4S-hydroxylating)

Comments:

Requires Fe²⁺ and ascorbate. The enzyme has been characterized from the bacterium Pantoea ananatis.

Links to other databases:

References:

[EC 1.14.11.75 created 2020]

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]

1.14.13.190

Transferred entry:

ferruginol synthase. Now EC 1.14.14.175, ferruginol synthase

[EC 1.14.13.190 created 2014, modified 2015, deleted 2020]

1.14.14.172

Accepted name:

3,5,6-trichloropyridin-2-ol monooxygenase

Reaction:

(1) 3,5,6-trichloropyridin-2-ol + FADH₂ + O₂ = 3,6-dichloropyridine-2,5-dione + Cl^- + FAD + H₂O
(2) 3,6-dichloropyridine-2,5-diol + FADH₂ + O₂ = 6-chloro-3-hydroxypyridine-2,5-dione + Cl^- + FAD + H₂O
(3) 6-chloropyridine-2,3,5-triol + FADH₂ + O₂ = 3,6-dihydroxypyridine-2,5-dione + Cl^- + FAD + H₂O

Other name(s):

tcpA (gene name)

Systematic name:

3,5,6-trichloropyridin-2-ol,FADH₂:oxygen oxidoreductase (dechlorinating)

Comments:

The enzyme, characterized from a number of bacterial species, participates in the degradation of 3,5,6-trichloropyridin-2-ol (TCP), a metabolite of the common organophosphorus insecticide chlorpyrifos. The enzyme is a multifunctional flavin-dependent monooxygenase that displaces three chlorine atoms by attacking three different positions in the substrate. Each reaction catalysed by the enzyme displaces a single chlorine and results in formation of a dione, which must be reduced by FADH₂ before the monooxygenase could catalyse the next step. The large amount of FADH₂ that is required is generated by a dedicated flavin reductase (TcpX). cf. EC 1.14.14.173, 2,4,6-trichlorophenol monooxygenase.

Links to other databases:

References:

1.	Li, J., Huang, Y., Hou, Y., Li, X., Cao, H. and Cui, Z. Novel gene clusters and metabolic pathway involved in 3,5,6-trichloro-2-pyridinol degradation by Ralstonia sp. strain T6. Appl. Environ. Microbiol. 79 (2013) 7445–7453. [PMID: 24056464]
2.	Fang, L., Shi, T., Chen, Y., Wu, X., Zhang, C., Tang, X., Li, Q.X. and Hua, R. Kinetics and catabolic pathways of the insecticide chlorpyrifos, annotation of the degradation genes, and characterization of enzymes TcpA and Fre in Cupriavidus nantongensis X1(T). J. Agric. Food Chem. 67 (2019) 2245–2254. [PMID: 30721044]

[EC 1.14.14.172 created 2020]

1.14.14.173

Accepted name:

2,4,6-trichlorophenol monooxygenase

Reaction:

2,4,6-trichlorophenol + FADH₂ + O₂ = 6-chloro-2-hydroxy-1,4-benzoquinone + 2 Cl^- + FAD (overall reaction)
(1a) 2,4,6-trichlorophenol + FADH₂ + O₂ = 2,6-dichloro-1,4-benzoquinone + Cl^- + FAD + H₂O
(1b) 2,6-dichloro-1,4-benzoquinone + H₂O = 6-chloro-2-hydroxy-1,4-benzoquinone + Cl^-

Other name(s):

tcpA (gene name)

Systematic name:

2,4,6-trichlorophenol,FADH₂:oxygen oxidoreductase (dechlorinating)

Comments:

The enzyme, characterized from Cupriavidus pinatubonensis, participates in the degradation of 2,4,6-trichlorophenol, a compound that has been used for decades as a wood preservative. The enzyme is a multifunctional flavin-dependent monooxygenase that catalyses two different reactions to displace two chlorine atoms, a monooxygenase reaction followed by a hydrolysis reaction that takes advantage of the reactivity of the product of the first reaction, 2,6-dichloro-1,4-benzoquinone [2]. The large amount of FADH₂ that is required is generated by a dedicated flavin reductase (TcpB). cf. EC 1.14.14.172, 3,5,6-trichloropyridin-2-ol monooxygenase.

Links to other databases:

References:

1.	Louie, T.M., Webster, C.M. and Xun, L. Genetic and biochemical characterization of a 2,4,6-trichlorophenol degradation pathway in Ralstonia eutropha JMP134. J. Bacteriol. 184 (2002) 3492–3500. [PMID: 12057943]
2.	Xun, L. and Webster, C.M. A monooxygenase catalyzes sequential dechlorinations of 2,4,6-trichlorophenol by oxidative and hydrolytic reactions. J. Biol. Chem. 279 (2004) 6696–6700. [DOI] [PMID: 14662756]
3.	Hayes, R.P., Webb, B.N., Subramanian, A.K., Nissen, M., Popchock, A., Xun, L. and Kang, C. Structural and catalytic differences between two FADH₂-dependent monooxygenases: 2,4,5-TCP 4-monooxygenase (TftD) from Burkholderia cepacia AC1100 and 2,4,6-TCP 4-monooxygenase (TcpA) from Cupriavidus necator JMP134. Int. J. Mol. Sci. 13 (2012) 9769–9784. [DOI] [PMID: 22949829]

[EC 1.14.14.173 created 2020, modified 2022]

1.14.14.174

Accepted name:

geranylhydroquinone 3′′-hydroxylase

Reaction:

geranylhydroquinone + [reduced NADPH—hemoprotein reductase] + O₂ = 3′′-hydroxygeranylhydroquinone + [oxidized NADPH—hemoprotein reductase] + H₂O

Glossary:

3′′-hydroxygeranylhydroquinone = 2-[(2Z)-3-(hydroxymethyl)-7-methylocta-2,6-dien-1-yl]benzene-1,4-diol

Other name(s):

GHQ 3′′-hydroxylase; CYP76B74 (gene name); geranylhydroquinone,NADPH:oxygen oxidoreductase (3′′-hydroxylating)

Systematic name:

geranylhydroquinone,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (3′′-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein found in plants, where it is part of the biosynthesis pathway of the red naphthoquinone pigment shikonin.

Links to other databases:

References:

1.	Yamamoto, H., Inoue, K., Li, S.M. and Heide, L. Geranylhydroquinone 3′′-hydroxylase, a cytochrome P-450 monooxygenase from Lithospermum erythrorhizon cell suspension cultures. Planta 210 (2000) 312–317. [DOI] [PMID: 10664138]
2.	Wang, S., Wang, R., Liu, T., Lv, C., Liang, J., Kang, C., Zhou, L., Guo, J., Cui, G., Zhang, Y., Werck-Reichhart, D., Guo, L. and Huang, L. CYP76B74 catalyzes the 3′′-hydroxylation of geranylhydroquinone in shikonin biosynthesis. Plant Physiol. 179 (2019) 402–414. [PMID: 30498024]

[EC 1.14.14.174 created 2010 as EC 1.14.13.116, transferred 2020 to EC 1.14.14.174]

1.14.14.175

Accepted name:

ferruginol synthase

Reaction:

abieta-8,11,13-triene + [reduced NADPH—hemoprotein reductase] + O₂ = ferruginol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of abietane diterpenoids biosynthesis, click here

Glossary:

ferruginol = abieta-8,11,13-trien-12-ol

Other name(s):

miltiradiene oxidase (incorrect); CYP76AH1; miltiradiene,NADPH:oxygen oxidoreductase (ferruginol forming) (incorrect)

Systematic name:

abieta-8,11,13-triene,[reduced NADPH—hemoprotein reductase]:oxygen 12-oxidoreductase (ferruginol-forming)

Comments:

A cytochrome P-450 (heme thiolate) enzyme found in some members of the Lamiaceae (mint family). The enzyme from Rosmarinus officinalis (rosemary) is involved in biosynthesis of carnosic acid, while the enzyme from the Chinese medicinal herb Salvia miltiorrhiza is involved in the biosynthesis of the tanshinones, abietane-type norditerpenoid naphthoquinones that are the main lipophilic bioactive components found in the plant.

Links to other databases:

References:

1.	Guo, J., Zhou, Y.J., Hillwig, M.L., Shen, Y., Yang, L., Wang, Y., Zhang, X., Liu, W., Peters, R.J., Chen, X., Zhao, Z.K. and Huang, L. CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts. Proc. Natl. Acad. Sci. USA 110 (2013) 12108–12113. [DOI] [PMID: 23812755]
2.	Zi, J. and Peters, R.J. Characterization of CYP76AH4 clarifies phenolic diterpenoid biosynthesis in the Lamiaceae. Org. Biomol. Chem. 11 (2013) 7650–7652. [DOI] [PMID: 24108414]
3.	Bozic, D., Papaefthimiou, D., Bruckner, K., de Vos, R.C., Tsoleridis, C.A., Katsarou, D., Papanikolaou, A., Pateraki, I., Chatzopoulou, F.M., Dimitriadou, E., Kostas, S., Manzano, D., Scheler, U., Ferrer, A., Tissier, A., Makris, A.M., Kampranis, S.C. and Kanellis, A.K. Towards elucidating carnosic acid biosynthesis in Lamiaceae: functional characterization of the three first steps of the pathway in Salvia fruticosa and Rosmarinus officinalis. PLoS One 10:e0124106 (2015). [DOI] [PMID: 26020634]

[EC 1.14.14.175 created 2014 as EC 1.14.13.190, modified 2015, transferred 2020 to EC 1.14.14.175]

1.14.14.176

Accepted name:

taxadiene 5α-hydroxylase

Reaction:

taxa-4,11-diene + [reduced NADPH—hemoprotein reductase] + O₂ = taxa-4(20),11-dien-5α-ol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of taxadiene hydroxylation, click here

Systematic name:

taxa-4,11-diene,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (5α-hydroxylating)

Comments:

This microsomal cytochrome-P-450 (heme-thiolate) enzyme is involved in the biosynthesis of the diterpenoid antineoplastic drug taxol (paclitaxel). The reaction includes rearrangement of the 4(5)-double bond to a 4(20)-double bond, possibly through allylic oxidation.

Links to other databases:

BRENDA, EXPASY, KEGG, PDB, CAS registry number: 9035-51-2

References:

1.	Hefner, J., Rubenstein, S.M., Ketchum, R.E., Gibson, D.M., Williams, R.M. and Croteau, R. Cytochrome P₄₅₀-catalyzed hydroxylation of taxa-4(5),11(12)-diene to taxa-4(20),11(12)-dien-5α-ol: the first oxygenation step in taxol biosynthesis. Chem. Biol. 3 (1996) 479–489. [DOI] [PMID: 8807878]

[EC 1.14.14.176 created 2002 as 1.14.99.37, transferred 2020 to EC 1.14.14.176]

1.14.16.3

Deleted entry:

anthranilate 3-monooxygenase. Withdrawn owing to insufficient evidence.

[EC 1.14.16.3 created 1972, deleted 2020]

1.14.19.77

Accepted name:

plasmanylethanolamine desaturase

Reaction:

a plasmanylethanolamine + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = a plasmenylethanolamine + 2 ferricytochrome b₅ + 2 H₂O

Glossary:

a plasmanylethanolamine = a 2-acyl-1-alkyl-sn-glycero-3-phosphoethanolamine

Other name(s):

TMEM189 (gene name); 2-acyl-1-alkyl-sn-glycero-3-phosphoethanolamine desaturase; alkylacylglycerophosphoethanolamine desaturase; alkylacylglycero-phosphorylethanolamine dehydrogenase; alkyl-acylglycerophosphorylethanolamine dehydrogenase; 1-O-alkyl-2-acyl-sn-glycero-3-phosphorylethanolamine desaturase; 1-O-alkyl 2-acyl-sn-glycero-3-phosphorylethanolamine desaturase

Systematic name:

plasmanylethanolamine,ferrocytochrome b₅:oxygen oxidoreductase (plasmenylethanolamine-forming)

Comments:

The enzyme catalyses the introduction of a double bond at position 1 of the alkyl group attached by an ether bond at the sn-1 position of plasmanylethanolamine, generating a vinyl ether-containing plasmenylethanolamine. The enzyme is found in animals and some bacteria, but not in plants, fungi, or most aerobic bacteria.

Links to other databases:

References:

1.	Stoffel, W. and LeKim, D. Studies on the biosynthesis of plasmalogens. Precursors in the biosynthesis of plasmalogens: on the stereospecificity of the biochemical dehydrogenation of the 1-O-alkyl glyceryl to the 1-O-alk-1′-enyl glyceryl ether bond. Hoppe-Seylers Z. Physiol. Chem. 352 (1971) 501–511. [PMID: 5550967]
2.	Paltauf, F. Biosynthesis of plasmalogens from alkyl- and alkyl-acyl-glycerophosphoryl ethanolamine in the rat brain. FEBS Lett. 17 (1971) 118–120. [PMID: 11946011]
3.	Paltuaf, F., Prough, R.A., Masters, B.S. and Johnston, J.M. Evidence for the participation of cytochrome b₅ in plasmalogen biosynthesis. J. Biol. Chem. 249 (1974) 2661–2662. [PMID: 4150797]
4.	Wykle, R.L. and Schremmer Lockmiller, J.M. The biosynthesis of plasmalogens by rat brain: involvement of the microsomal electron transport system. Biochim. Biophys. Acta 380 (1975) 291–298. [PMID: 235322]
5.	Gallego-Garcia, A., Monera-Girona, A.J., Pajares-Martinez, E., Bastida-Martinez, E., Perez-Castano, R., Iniesta, A.A., Fontes, M., Padmanabhan, S. and Elias-Arnanz, M. A bacterial light response reveals an orphan desaturase for human plasmalogen synthesis. Science 366 (2019) 128–132. [PMID: 31604315]

[EC 1.14.19.77 created 1976 as EC 1.14.99.19, transferred 2020 to EC 1.14.19.77]

1.14.99.19

Transferred entry:

plasmanylethanolamine desaturase. Now classified as EC 1.14.19.77, plasmanylethanolamine desaturase

[EC 1.14.99.19 created 1976, deleted 2020]

1.14.99.37

Transferred entry:

taxadiene 5α-hydroxylase. Now EC 1.14.14.176, taxadiene 5α-hydroxylase

[EC 1.14.99.37 created 2002, deleted 2020]

1.16.1.3

Deleted entry:

aquacobalamin reductase. This entry has been deleted since no specific enzyme catalysing this activity has been identified and it has been shown that aquacobalamin is efficiently reduced by free dihydroflavins and by non-specific reduced flavoproteins.

[EC 1.16.1.3 created 1972 as EC 1.6.99.8, transferred 2002 to EC 1.16.1.3, modified 2020, deleted 2020]

1.16.1.5

Deleted entry:

aquacobalamin reductase (NADPH). This entry has been deleted since the enzyme the entry was based on was later shown to be EC 1.2.1.51, pyruvate dehydrogenase (NADP⁺). On the other hand, it has been shown that non-enzymatic reduction of cob(III)alamin to cob(II)alamin occurs efficiently in the presence of free dihydroflavins or non-specific reduced flavoproteins.

[EC 1.16.1.5 created 1989 as EC 1.6.99.11, transferred 2002 to EC 1.16.1.5, modified 2020, deleted 2020]

1.17.9.2

Accepted name:

(+)-pinoresinol hydroxylase

Reaction:

(+)-pinoresinol + 2 oxidized azurin + H₂O = (+)-6-hydroxypinoresinol + 2 reduced azurin + 2 H⁺

Other name(s):

pinoresinol α-hydroxylase; pinAB (gene names)

Systematic name:

(+)-pinoresinol:azurin oxidoreductase

Comments:

Contains FAD. This enzyme, characterized from the bacterium Pseudomonas sp. SG-MS2, catalyses the incorporation of an oxygen atom originating from a water molecule into position C-6 of the lignan (+)-pinoresinol. The enzyme consists of a flavoprotein subunit and a c-type cytochrome subunit. Electrons that originate in the substrate are transferred via the FAD cofactor and the cytochrome subunit to the blue-copper protein azurin.

Links to other databases:

References:

Shettigar, M., Balotra, S., Kasprzak, A., Pearce, S.L., Lacey, M.J., Taylor, M.C., Liu, J.W., Cahill, D., Oakeshott, J.G. and Pandey, G. Oxidative catabolism of (+)-pinoresinol is initiated by an unusual flavocytochrome encoded by translationally coupled genes within a cluster of (+)-pinoresinol-coinduced genes in Pseudomonas sp. strain SG-MS2. Appl. Environ. Microbiol. 86 (2020) e00375-20. [PMID: 32198167]

[EC 1.17.9.2 created 2020]

*EC

2.1.1.354

Accepted name:

[histone H3]-lysine⁴ N-trimethyltransferase

Reaction:

3 S-adenosyl-L-methionine + a [histone H3]-L-lysine⁴ = 3 S-adenosyl-L-homocysteine + a [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine⁴ (overall reaction)
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine⁴ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶-methyl-L-lysine⁴
(1b) S-adenosyl-L-methionine + a [histone H3]-N⁶-methyl-L-lysine⁴ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶,N⁶-dimethyl-L-lysine⁴
(1c) S-adenosyl-L-methionine + a [histone H3]-N⁶,N⁶-dimethyl-L-lysine⁴ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine⁴

Other name(s):

KMT2H (gene name); KMT3C (gene name); KMT3D (gene name); KMT3E (gene name); PRDM9 (gene name); MLL5 (gene name); ASH1L (gene name); SMYD1 (gene name); SMYD2 (gene name); SMYD3 (gene name)

Systematic name:

S-adenosyl-L-methionine:[histone H3]-L-lysine⁴ N⁶-trimethyltransferase

Comments:

This entry describes several enzymes that successively methylate the L-lysine⁴ residue of histone H3 (H3K4), ultimately generating a trimethylated form. These modifications influence the binding of chromatin-associated proteins. In most cases the trimethylation of this position is associated with gene activation. EC 2.1.1.364, [histone H3]-lysine⁴ N-methyltransferase, describes enzymes that can catalyse only monomethylation of this substrate (the first sub-reaction of this entry); EC 2.1.1.370, [histone H3]-lysine⁴ N-dimethyltransferase, describes enzymes that catalyse only dimethylation of this substrate (the first two sub-reactions of this entry)

Links to other databases:

References:

1.	Nakamura, T., Mori, T., Tada, S., Krajewski, W., Rozovskaia, T., Wassell, R., Dubois, G., Mazo, A., Croce, C.M. and Canaani, E. ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. Mol. Cell 10 (2002) 1119–1128. [PMID: 12453419]
2.	Hamamoto, R., Furukawa, Y., Morita, M., Iimura, Y., Silva, F.P., Li, M., Yagyu, R. and Nakamura, Y. SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat. Cell Biol. 6 (2004) 731–740. [PMID: 15235609]
3.	Blazer, L.L., Lima-Fernandes, E., Gibson, E., Eram, M.S., Loppnau, P., Arrowsmith, C.H., Schapira, M. and Vedadi, M. PR domain-containing protein 7 (PRDM7) is a histone 3 lysine 4 trimethyltransferase. J. Biol. Chem. 291 (2016) 13509–13519. [PMID: 27129774]

[EC 2.1.1.354 created 1976 as EC 2.1.1.43, modified 1982, modified 1983, part transferred 2019 to EC 2.1.1.354, modified 2020]

*EC

2.1.1.355

Accepted name:

[histone H3]-lysine⁹ N-trimethyltransferase

Reaction:

3 S-adenosyl-L-methionine + a [histone H3]-L-lysine⁹ = 3 S-adenosyl-L-homocysteine + a [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine⁹ (overall reaction)
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine⁹ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶-methyl-L-lysine⁹
(1b) S-adenosyl-L-methionine + a [histone H3]-N⁶-methyl-L-lysine⁹ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶,N⁶-dimethyl-L-lysine⁹
(1c) S-adenosyl-L-methionine + a [histone H3]-N⁶,N⁶-dimethyl-L-lysine⁹ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine⁹

Other name(s):

KMT1A (gene name); KMT1B (gene name); KMT1C (gene name); KMT1D (gene name); KMT1F (gene name); MT8 (gene name); SUV39H1 (gene name); G9A (gene name); EHMT1 (gene name); PRDM2 (gene name)

Systematic name:

S-adenosyl-L-methionine:[histone H3]-L-lysine⁹ N⁶-trimethyltransferase

Comments:

This entry describes several enzymes that successively methylate the L-lysine⁹ residue of histone H3 (H3K9), ultimately generating a trimethylated form. These modifications influence the binding of chromatin-associated proteins. In general, the methylation of H3K9 leads to transcriptional repression of the affected target genes. cf. EC 2.1.1.367, [histone H3]-lysine⁹ N-methyltransferase, EC 2.1.1.368, [histone H3]-lysine⁹ N-dimethyltransferase, and EC 2.1.1.366, [histone H3]-N⁶,N⁶-dimethyl-lysine⁹ N-methyltransferase.

Links to other databases:

References:

1.	O'Carroll, D., Scherthan, H., Peters, A.H., Opravil, S., Haynes, A.R., Laible, G., Rea, S., Schmid, M., Lebersorger, A., Jerratsch, M., Sattler, L., Mattei, M.G., Denny, P., Brown, S.D., Schweizer, D. and Jenuwein, T. Isolation and characterization of Suv39h2, a second histone H3 methyltransferase gene that displays testis-specific expression. Mol. Cell Biol. 20 (2000) 9423–9433. [PMID: 11094092]
2.	Schotta, G., Ebert, A., Krauss, V., Fischer, A., Hoffmann, J., Rea, S., Jenuwein, T., Dorn, R. and Reuter, G. Central role of Drosophila SU(VAR)₃-9 in histone H3-K9 methylation and heterochromatic gene silencing. EMBO J. 21 (2002) 1121–1131. [PMID: 11867540]
3.	Tachibana, M., Sugimoto, K., Nozaki, M., Ueda, J., Ohta, T., Ohki, M., Fukuda, M., Takeda, N., Niida, H., Kato, H. and Shinkai, Y. G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev. 16 (2002) 1779–1791. [PMID: 12130538]
4.	Schultz, D.C., Ayyanathan, K., Negorev, D., Maul, G.G. and Rauscher, F.J., 3rd. SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev. 16 (2002) 919–932. [PMID: 11959841]
5.	Kim, K.C., Geng, L. and Huang, S. Inactivation of a histone methyltransferase by mutations in human cancers. Cancer Res. 63 (2003) 7619–7623. [PMID: 14633678]
6.	Wu, H., Min, J., Lunin, V.V., Antoshenko, T., Dombrovski, L., Zeng, H., Allali-Hassani, A., Campagna-Slater, V., Vedadi, M., Arrowsmith, C.H., Plotnikov, A.N. and Schapira, M. Structural biology of human H₃K9 methyltransferases. PLoS One 5:e8570 (2010). [PMID: 20084102]

[EC 2.1.1.355 created 1976 as EC 2.1.1.43, modified 1982, modified 1983, part transferred 2019 to EC 2.1.1.355, modified 2020]

*EC

2.1.1.356

Accepted name:

[histone H3]-lysine²⁷ N-trimethyltransferase

Reaction:

3 S-adenosyl-L-methionine + a [histone H3]-L-lysine²⁷ = 3 S-adenosyl-L-homocysteine + a [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine²⁷ (overall reaction)
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine²⁷ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶-methyl-L-lysine²⁷
(1b) S-adenosyl-L-methionine + a [histone H3]-N⁶-methyl-L-lysine²⁷ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶,N⁶-dimethyl-L-lysine²⁷
(1c) S-adenosyl-L-methionine + a [histone H3]-N⁶,N⁶-dimethyl-L-lysine²⁷ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine²⁷

Other name(s):

KMT6A (gene name); KMT6B (gene name); EZH1 (gene name); EZH₂ (gene name)

Systematic name:

S-adenosyl-L-methionine:[histone H3]-L-lysine²⁷ N⁶-trimethyltransferase

Comments:

This entry describes enzymes that successively methylate the L-lysine²⁷ residue of histone H3 (H3K27), ultimately generating a trimethylated form. These modifications influence the binding of chromatin-associated proteins. The methylation of lysine²⁷ leads to transcriptional repression of the affected target genes. The enzyme associates with other proteins to form a complex that is essential for activity. The enzyme can also methylate some non-histone proteins. cf. EC 2.1.1.369, [histone H3]-lysine²⁷ N-methyltransferase and EC 2.1.1.371, [histone H3]-lysine²⁷ N-dimethyltransferase.

Links to other databases:

References:

1.	Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R.S. and Zhang, Y. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298 (2002) 1039–1043. [PMID: 12351676]
2.	Kuzmichev, A., Nishioka, K., Erdjument-Bromage, H., Tempst, P. and Reinberg, D. Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev. 16 (2002) 2893–2905. [PMID: 12435631]
3.	Kirmizis, A., Bartley, S.M., Kuzmichev, A., Margueron, R., Reinberg, D., Green, R. and Farnham, P.J. Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27. Genes Dev. 18 (2004) 1592–1605. [PMID: 15231737]
4.	Schlesinger, Y., Straussman, R., Keshet, I., Farkash, S., Hecht, M., Zimmerman, J., Eden, E., Yakhini, Z., Ben-Shushan, E., Reubinoff, B.E., Bergman, Y., Simon, I. and Cedar, H. Polycomb-mediated methylation on Lys²⁷ of histone H3 pre-marks genes for de novo methylation in cancer. Nat. Genet. 39 (2007) 232–236. [PMID: 17200670]
5.	Shen, X., Liu, Y., Hsu, Y.J., Fujiwara, Y., Kim, J., Mao, X., Yuan, G.C. and Orkin, S.H. EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol. Cell 32 (2008) 491–502. [PMID: 19026780]
6.	Ezhkova, E., Lien, W.H., Stokes, N., Pasolli, H.A., Silva, J.M. and Fuchs, E. EZH1 and EZH2 cogovern histone H3K27 trimethylation and are essential for hair follicle homeostasis and wound repair. Genes Dev. 25 (2011) 485–498. [PMID: 21317239]

[EC 2.1.1.356 created 1976 as EC 2.1.1.43, modified 1982, modified 1983, part transferred 2019 to EC 2.1.1.356, modified 2020]

2.1.1.358

Deleted entry:

[histone H3]-dimethyl-L-lysine³⁶ N-methyltransferase. Now known to have the activity of 2.1.1.359, [histone H3]-lysine³⁶ N-trimethyltransferase.

[EC 2.1.1.358 created 1976 as EC 2.1.1.43, modified 1982, modified 1983, part transferred 2019 to EC 2.1.1.358, deleted 2020]

2.1.1.364

Accepted name:

[histone H3]-lysine⁴ N-methyltransferase

Reaction:

S-adenosyl-L-methionine + a [histone H3]-L-lysine⁴ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶-methyl-L-lysine⁴

Other name(s):

KMT7 (gene name); SETD7 (gene name); SET7/9 (gene name); KIAA1717 (gene name); KMT2A (gene name); KMT2B (gene name); KMT2C (gene name); KMT2D (gene name); KMT2F (gene name); KMT2G (gene name); MLL1 (gene name); MLL2 (gene name); MLL3 (gene name); MLL4 (gene name); SETD1A (gene name)

Systematic name:

S-adenosyl-L-methionine:[histone H3]-L-lysine⁴ N⁶-methyltransferase

Comments:

This entry describes enzymes that catalyse a single methylation of the L-lysine⁴ residue of histone H3 (H3K4), generating a monomethylated form. This modifications influence the binding of chromatin-associated proteins and result in gene activation or suppression. Some enzymes that catalyse this reaction continue to generate a dimethyated form, these enzymes are classified under EC 2.1.1.370, [histone H3]-lysine⁴ N-dimethyltransferase. Other enzymes continue to catalyse a third methylation, those are classified under EC 2.1.1.354, [histone H3]-lysine⁴ N-trimethyltransferase.

Links to other databases:

References:

1.	Wang, H., Cao, R., Xia, L., Erdjument-Bromage, H., Borchers, C., Tempst, P. and Zhang, Y. Purification and functional characterization of a histone H3-lysine 4-specific methyltransferase. Mol. Cell 8 (2001) 1207–1217. [PMID: 11779497]
2.	Nishioka, K., Chuikov, S., Sarma, K., Erdjument-Bromage, H., Allis, C.D., Tempst, P. and Reinberg, D. Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation. Genes Dev. 16 (2002) 479–489. [PMID: 11850410]
3.	Wilson, J.R., Jing, C., Walker, P.A., Martin, S.R., Howell, S.A., Blackburn, G.M., Gamblin, S.J. and Xiao, B. Crystal structure and functional analysis of the histone methyltransferase SET7/9. Cell 111 (2002) 105–115. [PMID: 12372304]
4.	Xiao, B., Jing, C., Wilson, J.R., Walker, P.A., Vasisht, N., Kelly, G., Howell, S., Taylor, I.A., Blackburn, G.M. and Gamblin, S.J. Structure and catalytic mechanism of the human histone methyltransferase SET7/9. Nature 421 (2003) 652–656. [PMID: 12540855]
5.	Hu, P. and Zhang, Y. Catalytic mechanism and product specificity of the histone lysine methyltransferase SET7/9: an ab initio QM/MM-FE study with multiple initial structures. J. Am. Chem. Soc. 128 (2006) 1272–1278. [PMID: 16433545]
6.	Patel, A., Dharmarajan, V., Vought, V.E. and Cosgrove, M.S. On the mechanism of multiple lysine methylation by the human mixed lineage leukemia protein-1 (MLL1) core complex. J. Biol. Chem. 284 (2009) 24242–24256. [DOI] [PMID: 19556245]
7.	Shinsky, S.A., Monteith, K.E., Viggiano, S. and Cosgrove, M.S. Biochemical reconstitution and phylogenetic comparison of human SET1 family core complexes involved in histone methylation. J. Biol. Chem. 290 (2015) 6361–6375. [DOI] [PMID: 25561738]

[EC 2.1.1.364 created 1976 as EC 2.1.1.43, modified 1982, modified 1983, part transferred 2020 to EC 2.1.1.354]

2.1.1.365

Accepted name:

MMP 1-O-methyltransferase

Reaction:

S-adenosyl-L-methionine + 3,3′-di-O-methyl-4α-mannobiose = S-adenosyl-L-homocysteine + 1,3,3′-tri-O-methyl-4α-mannobiose

Glossary:

3,3′-di-O-methyl-4α-mannobiose = 3-O-methyl-α-D-mannopyranosyl-(1→4)-3-O-methyl-α-D-mannopyranose

Other name(s):

MeT1; 3-O-methylmannose polysaccharide 1-O-methyltransferase

Systematic name:

S-adenosyl-L-methionine:3,3′-di-O-methyl-4α-mannobiose 1-O-methyltransferase

Comments:

Requires Mg²⁺. The enzyme, characterized from the bacterium Mycolicibacterium hassiacum, participates in the biosynthesis of 3-O-methylmannose polysaccharides (MMP), which are intracellular polymethylated polysaccharides implicated in the modulation of fatty acid metabolism in nontuberculous mycobacteria. The methylation catalysed by this enzyme was shown to block the reducing end of 3,3′-di-O-methyl-α-mannobiose, a probable early precursor of the 3-O-methylmannose polysaccharides.

Links to other databases:

References:

Ripoll-Rozada, J., Costa, M., Manso, J.A., Maranha, A., Miranda, V., Sequeira, A., Ventura, M.R., Macedo-Ribeiro, S., Pereira, P.JB. and Empadinhas, N. Biosynthesis of mycobacterial methylmannose polysaccharides requires a unique 1-O-methyltransferase specific for 3-O-methylated mannosides. Proc. Natl. Acad. Sci. USA 116 (2019) 835–844. [DOI] [PMID: 30606802]

[EC 2.1.1.365 created 2020]

2.1.1.366

Accepted name:

[histone H3]-N⁶,N⁶-dimethyl-lysine⁹ N-methyltransferase

Reaction:

S-adenosyl-L-methionine + a [histone H3]-N⁶,N⁶-dimethyl-L-lysine⁹ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine⁹

Other name(s):

KMT1E (gene name); SETDB1 (gene name); KIAA0067 (gene name)

Systematic name:

S-adenosyl-L-methionine:[histone H3]-N⁶,N⁶-dimethyl-L-lysine⁹ N⁶-methyltransferase

Comments:

The enzyme methylates only dimethylated lysine⁹ of histone H3 (H3K9), forming the trimethylated form. This modification influences the binding of chromatin-associated proteins. In general, the methylation of H3K9 leads to transcriptional repression of the affected target genes. The enzyme is highly upregulated in Huntington disease patients. cf. EC 2.1.1.367, [histone H3]-lysine⁹ N-methyltransferase, and EC 2.1.1.368, [histone H3]-lysine⁹ N-dimethyltransferase, and EC 2.1.1.355, [histone H3]-lysine⁹ N-trimethyltransferase.

Links to other databases:

References:

1.	Yang, L., Xia, L., Wu, D.Y., Wang, H., Chansky, H.A., Schubach, W.H., Hickstein, D.D. and Zhang, Y. Molecular cloning of ESET, a novel histone H3-specific methyltransferase that interacts with ERG transcription factor. Oncogene 21 (2002) 148–152. [PMID: 11791185]
2.	Wang, H., An, W., Cao, R., Xia, L., Erdjument-Bromage, H., Chatton, B., Tempst, P., Roeder, R.G. and Zhang, Y. mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of histone H3 to cause transcriptional repression. Mol. Cell 12 (2003) 475–487. [PMID: 14536086]
3.	Pinheiro, I., Margueron, R., Shukeir, N., Eisold, M., Fritzsch, C., Richter, F.M., Mittler, G., Genoud, C., Goyama, S., Kurokawa, M., Son, J., Reinberg, D., Lachner, M. and Jenuwein, T. Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity. Cell 150 (2012) 948–960. [PMID: 22939622]

[EC 2.1.1.366 created 2020]

2.1.1.367

Accepted name:

[histone H3]-lysine⁹ N-methyltransferase

Reaction:

S-adenosyl-L-methionine + a [histone H3]-L-lysine⁹ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶-methyl-L-lysine⁹

Other name(s):

PRDM3 (gene name); PRDM16 (gene name)

Systematic name:

S-adenosyl-L-methionine:[histone H3]-L-lysine⁹ N⁶-methyltransferase

Comments:

This entry describes several enzymes that methylate the L-lysine-9 residue of histone H3 (H3K9) only once, generating a monomethylated form. These modifications influence the binding of chromatin-associated proteins. cf. EC 2.1.1.368, [histone H3]-lysine⁹ N-dimethyltransferase, EC 2.1.1.355, [histone H3]-lysine⁹ N-trimethyltransferase, and EC 2.1.1.366, [histone H3]-N⁶,N⁶-dimethyl-lysine⁹ N-methyltransferase.

Links to other databases:

References:

Pinheiro, I., Margueron, R., Shukeir, N., Eisold, M., Fritzsch, C., Richter, F.M., Mittler, G., Genoud, C., Goyama, S., Kurokawa, M., Son, J., Reinberg, D., Lachner, M. and Jenuwein, T. Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity. Cell 150 (2012) 948–960. [PMID: 22939622]

[EC 2.1.1.367 created 2020]

2.1.1.368

Accepted name:

[histone H3]-lysine⁹ N-dimethyltransferase

Reaction:

2 S-adenosyl-L-methionine + a [histone H3]-L-lysine⁹ = 2 S-adenosyl-L-homocysteine + a [histone H3]-N⁶,N⁶-dimethyl-L-lysine⁹ (overall reaction)
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine⁹ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶-methyl-L-lysine⁹
(1b) S-adenosyl-L-methionine + a [histone H3]-N⁶-methyl-L-lysine⁹ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶,N⁶-dimethyl-L-lysine⁹

Other name(s):

SUVH1 (gene name); SUVR1 (gene name); SET32 (gene name); SDG32 (gene name); SET13 (gene name)

Systematic name:

S-adenosyl-L-methionine:[histone H3]-L-lysine⁹ N⁶-dimethyltransferase

Comments:

This entry describes several enzymes, characterized from plants, that successively methylate the L-lysine-9 residue of histone H3 (H3K9) twice, ultimately generating a dimethylated form. These modifications influence the binding of chromatin-associated proteins. In general, the methylation of H3K9 leads to transcriptional repression of the affected target genes. cf. EC 2.1.1.367, [histone H3]-lysine⁹ N-methyltransferase, EC 2.1.1.366, [histone H3]-N⁶,N⁶-dimethyl-lysine⁹ N-methyltransferase, and EC 2.1.1.355, [histone H3]-lysine⁹ N-trimethyltransferase.

Links to other databases:

References:

1.	Yu, Y., Dong, A. and Shen, W.H. Molecular characterization of the tobacco SET domain protein NtSET1 unravels its role in histone methylation, chromatin binding, and segregation. Plant J. 40 (2004) 699–711. [PMID: 15546353]
2.	Shen, W.H. and Meyer, D. Ectopic expression of the NtSET1 histone methyltransferase inhibits cell expansion, and affects cell division and differentiation in tobacco plants. Plant Cell Physiol. 45 (2004) 1715–1719. [PMID: 15574848]
3.	Naumann, K., Fischer, A., Hofmann, I., Krauss, V., Phalke, S., Irmler, K., Hause, G., Aurich, A.C., Dorn, R., Jenuwein, T. and Reuter, G. Pivotal role of AtSUVH₂ in heterochromatic histone methylation and gene silencing in Arabidopsis. EMBO J. 24 (2005) 1418–1429. [PMID: 15775980]

[EC 2.1.1.368 created 2020]

2.1.1.369

Accepted name:

[histone H3]-lysine²⁷ N-methyltransferase

Reaction:

S-adenosyl-L-methionine + a [histone H3]-L-lysine²⁷ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶-methyl-L-lysine²⁷

Other name(s):

ATXR5 (gene name)

Systematic name:

S-adenosyl-L-methionine:[histone H3]-L-lysine²⁷ N⁶-methyltransferase

Comments:

This entry describes enzymes that methylate the L-lysine-27 residue of histone H3 only once, generating a monomethylated form. This modification influences the binding of chromatin-associated proteins. The methylation of lysine-27 leads to transcriptional repression of the affected target genes. cf. EC 2.1.1.371, [histone H3]-lysine²⁷ N-dimethyltransferase, and EC 2.1.1.356, [histone H3]-lysine²⁷ N-trimethyltransferase.

Links to other databases:

References:

Jacob, Y., Feng, S., LeBlanc, C.A., Bernatavichute, Y.V., Stroud, H., Cokus, S., Johnson, L.M., Pellegrini, M., Jacobsen, S.E. and Michaels, S.D. ATXR5 and ATXR6 are H3K27 monomethyltransferases required for chromatin structure and gene silencing. Nat. Struct. Mol. Biol. 16 (2009) 763–768. [PMID: 19503079]

[EC 2.1.1.369 created 2020]

2.1.1.370

Accepted name:

[histone H3]-lysine⁴ N-dimethyltransferase

Reaction:

2 S-adenosyl-L-methionine + a [histone H3]-L-lysine⁴ = 2 S-adenosyl-L-homocysteine + a [histone H3]-N⁶,N⁶-dimethyl-L-lysine⁴ (overall reaction)
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine⁴ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶-methyl-L-lysine⁴
(1b) S-adenosyl-L-methionine + a [histone H3]-N⁶-methyl-L-lysine⁴ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶,N⁶-dimethyl-L-lysine⁴

Other name(s):

NSD3 (gene name)

Systematic name:

S-adenosyl-L-methionine:[histone H3]-L-lysine⁴ N⁶-dimethyltransferase

Comments:

This entry describes enzymes that successively methylate the L-lysine⁴ residue of histone H3 (H3K4) twice, ultimately generating a dimethylated form. These modifications influence the binding of chromatin-associated proteins. The human NSD3 protein also catalyses the activity of EC 2.1.1.371, [histone H3]-lysine²⁷ N-dimethyltransferase. cf. EC 2.1.1.364, [histone H3]-lysine⁴ N-methyltransferase, and EC 2.1.1.354, [histone H3]-lysine⁴ N-trimethyltransferase.

Links to other databases:

References:

1.	Kim, S.M., Kee, H.J., Eom, G.H., Choe, N.W., Kim, J.Y., Kim, Y.S., Kim, S.K., Kook, H., Kook, H. and Seo, S.B. Characterization of a novel WHSC1-associated SET domain protein with H3K4 and H3K27 methyltransferase activity. Biochem. Biophys. Res. Commun. 345 (2006) 318–323. [PMID: 16682010]

[EC 2.1.1.370 created 2020.]

2.1.1.371

Accepted name:

[histone H3]-lysine²⁷ N-dimethyltransferase

Reaction:

2 S-adenosyl-L-methionine + a [histone H3]-L-lysine²⁷ = 2 S-adenosyl-L-homocysteine + a [histone H3]-N⁶,N⁶-dimethyl-L-lysine²⁷ (overall reaction)
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine²⁷ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶-methyl-L-lysine²⁷
(1b) S-adenosyl-L-methionine + a [histone H3]-N⁶-methyl-L-lysine²⁷ = S-adenosyl-L-homocysteine + a [histone H3]-N⁶,N⁶-dimethyl-L-lysine²⁷

Other name(s):

NSD3 (gene name)

Systematic name:

S-adenosyl-L-methionine:[histone H3]-L-lysine²⁷ N⁶-dimethyltransferase

Comments:

This entry describes enzymes that successively methylate the L-lysine²⁷ residue of histone H3 (H3K27) twice, ultimately generating a dimethylated form. These modifications influence the binding of chromatin-associated proteins. The human NSD3 protein also catalyses the activity of EC 2.1.1.370, [histone H3]-lysine⁴ N-dimethyltransferase. cf. EC 2.1.1.369, [histone H3]-lysine²⁷ N-methyltransferase, and EC 2.1.1.356, [histone H3]-lysine²⁷ N-trimethyltransferase.

Links to other databases:

References:

1.	Kim, S.M., Kee, H.J., Eom, G.H., Choe, N.W., Kim, J.Y., Kim, Y.S., Kim, S.K., Kook, H., Kook, H. and Seo, S.B. Characterization of a novel WHSC1-associated SET domain protein with H3K4 and H3K27 methyltransferase activity. Biochem. Biophys. Res. Commun. 345 (2006) 318–323. [PMID: 16682010]

[EC 2.1.1.371 created 2020]

2.1.1.372

Accepted name:

[histone H4]-lysine²⁰ N-trimethyltransferase

Reaction:

3 S-adenosyl-L-methionine + a [histone H4]-L-lysine²⁰ = 3 S-adenosyl-L-homocysteine + a [histone H4]-N⁶,N⁶,N⁶-trimethyl-L-lysine²⁰ (overall reaction)
(1a) S-adenosyl-L-methionine + a [histone H4]-L-lysine²⁰ = S-adenosyl-L-homocysteine + a [histone H4]-N⁶-methyl-L-lysine²⁰
(1b) S-adenosyl-L-methionine + a [histone H4]-N⁶-methyl-L-lysine²⁰ = S-adenosyl-L-homocysteine + a [histone H4]-N⁶,N⁶-dimethyl-L-lysine²⁰
(1c) S-adenosyl-L-methionine + a [histone H4]-N⁶,N⁶-dimethyl-L-lysine²⁰ = S-adenosyl-L-homocysteine + a [histone H4]-N⁶,N⁶,N⁶-trimethyl-L-lysine²⁰

Other name(s):

SET9 (gene name)

Systematic name:

S-adenosyl-L-methionine:[histone H4]-L-lysine²⁰ N⁶-trimethyltransferase

Comments:

The enzyme, characterized from the fission yeast Schizosaccharomyces pombe, catalyses three successive methylations of the L-lysine-20 residue of histone H4 (H4K20), forming the trimethylated form. The methylation of this site is apparently not involved in the regulation of gene expression or heterochromatin function but participates in DNA damage response. cf. EC 2.1.1.361, [histone H4]-lysine²⁰ N-methyltransferase, and EC 2.1.1.362, [histone H4]-N-methyl-L-lysine²⁰ N-methyltransferase.

Links to other databases:

References:

1.	Sanders, S.L., Portoso, M., Mata, J., Bahler, J., Allshire, R.C. and Kouzarides, T. Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Cell 119 (2004) 603–614. [PMID: 15550243]

[EC 2.1.1.372 created 2020]

2.3.2.34

Accepted name:

E2 NEDD8-conjugating enzyme

Reaction:

[E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine = [E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine

Glossary:

NEDD = Neural-precursor-cell Expressed Developmentally Down-regulated protein

Other name(s):

NEDD8-carrier-protein E2; NEDD8-conjugating enzyme E2; UBE2M (gene name); UBE2F (gene name)

Systematic name:

[E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine:[E2 NEDD8-conjugating enzyme] [NEDD8-protein]-yl transferase

Comments:

Some RING-type E3 ubiquitin transferases (EC 2.3.2.27) are not able to bind a substrate protein directly. Instead, they form complexes with a cullin scaffold protein and a substrate recognition module, which are known as CRL (Cullin-RING-Ligase) complexes. The cullin protein needs to be activated by the ubiquitin-like protein NEDD8 in a process known as neddylation. Like ubiquitin, the NEDD8 protein ends with two glycine residues. EC 6.2.1.64, E1 NEDD8-activating enzyme, activates NEDD8 in an ATP-dependent reaction by forming a high-energy thioester intermediate between NEDD8 and one of its cysteine residues. The activated NEDD8 is subsequently transferred to a cysteine residue of an E2 NEDD8-conjugating enzyme, and is eventually conjugated to a lysine residue of specific substrates in the presence of the appropriate E3 transferase (EC 2.3.2.32, cullin-RING-type E3 NEDD8 transferase).

Links to other databases:

References:

1.	Osaka, F., Kawasaki, H., Aida, N., Saeki, M., Chiba, T., Kawashima, S., Tanaka, K. and Kato, S. A new NEDD8-ligating system for cullin-4A. Genes Dev. 12 (1998) 2263–2268. [PMID: 9694792]
2.	Gong, L. and Yeh, E.T. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J. Biol. Chem. 274 (1999) 12036–12042. [PMID: 10207026]
3.	Huang, D.T., Miller, D.W., Mathew, R., Cassell, R., Holton, J.M., Roussel, M.F. and Schulman, B.A. A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8. Nat. Struct. Mol. Biol. 11 (2004) 927–935. [PMID: 15361859]
4.	Huang, D.T., Ayrault, O., Hunt, H.W., Taherbhoy, A.M., Duda, D.M., Scott, D.C., Borg, L.A., Neale, G., Murray, P.J., Roussel, M.F. and Schulman, B.A. E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification. Mol. Cell 33 (2009) 483–495. [PMID: 19250909]

[EC 2.3.2.34 created 2020]

2.3.2.35

Accepted name:

capsaicin synthase

Reaction:

(6E)-8-methylnon-6-enoyl-CoA + vanillylamine = CoA + capsaicin

Other name(s):

CS (gene name) (ambiguous); Pun1 (locus name)

Systematic name:

(6E)-8-methylnon-6-enoyl-CoA:vanillylamine 8-methylnon-6-enoyltransferase

Comments:

The enzyme, found only in plants that belong to the Capsicum genus, catalyses the last step in the biosynthesis of capsaicinoids. The enzyme catalyses the acylation of vanillylamine by a branched-chain fatty acid. The exact structure of the fatty acid determines the type of capsaicinoid formed.

Links to other databases:

References:

1.	Blum, E., Liu, K., Mazourek, M., Yoo, E.Y., Jahn, M. and Paran, I. Molecular mapping of the C locus for presence of pungency in Capsicum. Genome 45 (2002) 702–705. [PMID: 12175073]
2.	Stewart, C., Jr., Kang, B.C., Liu, K., Mazourek, M., Moore, S.L., Yoo, E.Y., Kim, B.D., Paran, I. and Jahn, M.M. The Pun1 gene for pungency in pepper encodes a putative acyltransferase. Plant J. 42 (2005) 675–688. [PMID: 15918882]
3.	Kim, S., Park, M., Yeom, S.I., Kim, Y.M., Lee, J.M., Lee, H.A., Seo, E., Choi, J., Cheong, K., Kim, K.T., Jung, K., Lee, G.W., Oh, S.K., Bae, C., Kim, S.B., Lee, H.Y., Kim, S.Y., Kim, M.S., Kang, B.C., Jo, Y.D., Yang, H.B., Jeong, H.J., Kang, W.H., Kwon, J.K., Shin, C., Lim, J.Y., Park, J.H., Huh, J.H., Kim, J.S., Kim, B.D., Cohen, O., Paran, I., Suh, M.C., Lee, S.B., Kim, Y.K., Shin, Y., Noh, S.J., Park, J., Seo, Y.S., Kwon, S.Y., Kim, H.A., Park, J.M., Kim, H.J., Choi, S.B., Bosland, P.W., Reeves, G., Jo, S.H., Lee, B.W., Cho, H.T., Choi, H.S., Lee, M.S., Yu, Y., Do Choi, Y., Park, B.S., van Deynze, A., Ashrafi, H., Hill, T., Kim, W.T., Pai, H.S., Ahn, H.K., Yeam, I., Giovannoni, J.J., Rose, J.K., Sorensen, I., Lee, S.J., Kim, R.W., Choi, I.Y., Choi, B.S., Lim, J.S., Lee, Y.H. and Choi, D. Genome sequence of the hot pepper provides insights into the evolution of pungency in Capsicum species. Nat. Genet. 46 (2014) 270–278. [PMID: 24441736]

[EC 2.3.2.35 created 2020]

2.4.1.375

Accepted name:

rhamnogalacturonan I galactosyltransferase

Reaction:

Transfer of a β-galactosyl residue in a β-(1→4) linkage from UDP-α-D-galactose to rhamnosyl residues within the rhamnogalacturonan I backbone.

Glossary:

rhamnogalacturonan I backbone = [(1→2)-α-L-rhamnosyl-(1→4)-α-D-galacturonosyl]_n

Systematic name:

UDP-α-D-galactose:[rhamnogalacturonan I]-α-L-rhamnosyl β-1,4-galactosyltransferase (configuration-inverting)

Comments:

The enzyme, characterized from the plant Vigna angularis (azuki beans), participates in the biosynthesis of rhamnogalacturonan I, one of the components of pectin in plant cell wall. It does not require any metal ions, and prefers substrates with a degree of polymerization larger than 9.

Links to other databases:

References:

1.	Matsumoto, N., Takenaka, Y., Wachananawat, B., Kajiura, H., Imai, T. and Ishimizu, T. Rhamnogalacturonan I galactosyltransferase: Detection of enzyme activity and its hyperactivation. Plant Physiol. Biochem. 142 (2019) 173–178. [DOI] [PMID: 31299599]

[EC 2.4.1.375 created 2020]

2.4.1.376

Accepted name:

EGF-domain serine glucosyltransferase

Reaction:

UDP-α-D-glucose + [protein with EGF-like domain]-L-serine = UDP + [protein with EGF-like domain]-3-O-(β-D-glucosyl)-L-serine

Other name(s):

POGLUT1 (gene name) (ambiguous); rumi (gene name) (ambiguous)

Systematic name:

UDP-α-D-glucose:[protein with EGF-like domain]-L-serine O-β-glucosyltransferase (configuration-inverting)

Comments:

The enzyme, found in animals and insects, is involved in the biosynthesis of the α-D-xylosyl-(1→3)-α-D-xylosyl-(1→3)-β-D-glucosyl trisaccharide on epidermal growth factor-like (EGF-like) domains. Glycosylation takes place at the serine in the C-X-S-X-P-C motif. The enzyme is bifunctional also being active with UDP-α-xylose as donor (EC 2.4.2.63, EGF-domain serine xylosyltransferase). When present on Notch proteins, the trisaccharide functions as a modulator of the signalling activity of this protein.

Links to other databases:

References:

1.	Li, Z., Fischer, M., Satkunarajah, M., Zhou, D., Withers, S.G. and Rini, J.M. Structural basis of Notch O-glucosylation and O-xylosylation by mammalian protein-O-glucosyltransferase 1 (POGLUT1). Nat. Commun. 8:185 (2017). [PMID: 28775322]

[EC 2.4.1.376 created 2020]

2.4.2.62

Accepted name:

xylosyl α-1,3-xylosyltransferase

Reaction:

UDP-α-D-xylose + [protein with EGF-like domain]-3-O-[α-D-xylosyl-(1→3)-β-D-glucosyl]-L-serine = UDP + [protein with EGF-like domain]-3-O-[α-D-xylosyl-(1→3)-α-D-xylosyl-(1→3)-β-D-glucosyl]-L-serine

Other name(s):

XXYLT1 (gene name)

Systematic name:

UDP-α-D-xylose:[EGF-like domain protein]-3-O-[α-D-xylosyl-(1→3)-β-D-glucosyl]-L-serine 3-α-D-xylosyltransferase (configuration-retaining)

Comments:

The enzyme, found in animals and insects, is involved in the biosynthesis of the α-D-xylosyl-(1→3)-α-D-xylosyl-(1→3)-β-D-glucosyl trisaccharide on epidermal growth factor-like (EGF-like) domains. When present on Notch proteins, the trisaccharide functions as a modulator of the signalling activity of this protein.

Links to other databases:

References:

1.	Minamida, S., Aoki, K., Natsuka, S., Omichi, K., Fukase, K., Kusumoto, S. and Hase, S. Detection of UDP-D-xylose: α-D-xyloside α 1-→3xylosyltransferase activity in human hepatoma cell line HepG2. J. Biochem. 120 (1996) 1002–1006. [PMID: 8982869]
2.	Sethi, M.K., Buettner, F.F., Ashikov, A., Krylov, V.B., Takeuchi, H., Nifantiev, N.E., Haltiwanger, R.S., Gerardy-Schahn, R. and Bakker, H. Molecular cloning of a xylosyltransferase that transfers the second xylose to O-glucosylated epidermal growth factor repeats of notch. J. Biol. Chem. 287 (2012) 2739–2748. [PMID: 22117070]
3.	Yu, H., Takeuchi, M., LeBarron, J., Kantharia, J., London, E., Bakker, H., Haltiwanger, R.S., Li, H. and Takeuchi, H. Notch-modifying xylosyltransferase structures support an SNi-like retaining mechanism. Nat. Chem. Biol. 11 (2015) 847–854. [PMID: 26414444]

[EC 2.4.2.62 created 2020]

2.4.2.63

Accepted name:

EGF-domain serine xylosyltransferase

Reaction:

UDP-α-D-xylose + [protein with EGF-like domain]-L-serine = UDP + [protein with EGF-like domain]-3-O-(β-D-xylosyl)-L-serine

Other name(s):

POGLUT1 (gene name) (ambiguous); rumi (gene name) (ambiguous)

Systematic name:

UDP-α-D-xylose:[protein with EGF-like domain]-L-serine O-β-xylosyltransferase (configuration-inverting)

Comments:

The enzyme, found in animals and insects, xylosylates at the serine in the C-X-S-X-P-C motif of epidermal growth factor-like (EGF-like) domains. The enzyme is bifunctional also being active with UDP-α-glucose as donor (EC 2.4.1.376, EGF-domain serine glucosyltransferase).

Links to other databases:

References:

1.	Li, Z., Fischer, M., Satkunarajah, M., Zhou, D., Withers, S.G. and Rini, J.M. Structural basis of Notch O-glucosylation and O-xylosylation by mammalian protein-O-glucosyltransferase 1 (POGLUT1). Nat. Commun. 8:185 (2017). [PMID: 28775322]

[EC 2.4.2.63 created 2020]

2.4.99.22

Transferred entry:

N-acetylglucosaminide α-(2,6)-sialyltransferase. Now EC 2.4.3.10, N-acetylglucosaminide α-(2,6)-sialyltransferase

[EC 2.4.99.22 created 2020, deleted 2022]

*EC

2.6.1.23

Accepted name:

4-hydroxyglutamate transaminase

Reaction:

erythro-4-hydroxy-L-glutamate + 2-oxoglutarate = (4R)-4-hydroxy-2-oxoglutarate + L-glutamate

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

Glossary:

erythro-4-hydroxy-L-glutamate = (2S,4R)-2-amino-4-hydroxypentanedioate

Other name(s):

4-hydroxyglutamate aminotransferase; 4-hydroxy-L-glutamate:2-oxoglutarate aminotransferase

Systematic name:

erythro-4-hydroxy-L-glutamate:2-oxoglutarate aminotransferase

Comments:

The enzyme participates in a degradation pathway of trans-4-hydroxy-L-proline, a compound that contributes to the stability of the collagen triple helix. Oxaloacetate can replace 2-oxoglutarate. This enzyme may be identical with EC 2.6.1.1 aspartate transaminase.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 37277-86-4

References:

1.	Goldstone, A. and Adams, E. Metabolism of γ-hydroxyglutamic acid. I. Conversion to α-hydroxy-γ-ketoglutarate by purified glutamic-aspartic transaminase to rat liver. J. Biol. Chem. 237 (1962) 3476–3485. [PMID: 13948827]
2.	Kuratomi, K., Fukunaga, K. and Kobayashi, Y. The metabolism of γ-hydroxyglutamate in rat liver. II. A transaminase concerned in γ-hydroxyglutamate metabolism. Biochim. Biophys. Acta 78 (1963) 629–636. [DOI] [PMID: 14089443]
3.	Maitra U, Deekker E Purification of rat-liver γ-hydroxyglutamate transaminase and its probable identity with glutamate-aspartate transaminase. Biochim. Biophys. Acta 81 (1964) 517–532. [PMID: 14170323]

[EC 2.6.1.23 created 1972, modified 1982, modified 2020]

2.6.1.119

Accepted name:

vanillin aminotransferase

Reaction:

L-alanine + vanillin = pyruvate + vanillylamine

Other name(s):

VAMT (gene name)

Systematic name:

L-alanine:vanillin aminotransferase

Comments:

The enzyme participates in the biosynthesis of capsaicinoids in pungent cultivars of Capsicum sp. In vivo it has only been assayed in the reverse direction, where the preferred amino group acceptors were found to be pyruvate and oxaloacetate.

Links to other databases:

References:

1.	Curry, J., Aluru, M., Mendoza, M., Nevarez, J., Melendrez, M. and O'Connell, M.A. Transcripts for possible capsaicinoid biosynthetic genes are differentially accumulated in pungent and non-pungent Capsicum spp. Plant Sci. 148 (1999) 47–57.
2.	del Rosario Abraham-Juarez, M., del Carmen Rocha-Granados, M., Lopez, M.G., Rivera-Bustamante, R.F. and Ochoa-Alejo, N. Virus-induced silencing of Comt, pAmt and Kas genes results in a reduction of capsaicinoid accumulation in chili pepper fruits. Planta 227 (2008) 681–695. [PMID: 17999078]
3.	Lang, Y., Kisaka, H., Sugiyama, R., Nomura, K., Morita, A., Watanabe, T., Tanaka, Y., Yazawa, S. and Miwa, T. Functional loss of pAMT results in biosynthesis of capsinoids, capsaicinoid analogs, in Capsicum annuum cv. CH-19 Sweet. Plant J. 59 (2009) 953–961. [PMID: 19473323]
4.	Gururaj, H.B., Padma, M.N., Giridhar, P. and Ravishankar, G.A. Functional validation of Capsicum frutescens aminotransferase gene involved in vanillylamine biosynthesis using Agrobacterium mediated genetic transformation studies in Nicotiana tabacum and Capsicum frutescens calli cultures. Plant Sci. 195 (2012) 96–105. [PMID: 22921003]
5.	Weber, N., Ismail, A., Gorwa-Grauslund, M. and Carlquist, M. Biocatalytic potential of vanillin aminotransferase from Capsicum chinense. BMC Biotechnol 14:25 (2014). [PMID: 24712445]

[EC 2.6.1.119 created 2020]

*EC

2.7.1.48

Accepted name:

uridine/cytidine kinase

Reaction:

(1) ATP + uridine = ADP + UMP
(2) ATP + cytidine = ADP + CMP

Other name(s):

UCK (gene name); URK1 (gene name); pyrimidine ribonucleoside kinase; uridine-cytidine kinase; uridine kinase (phosphorylating); uridine phosphokinase; ATP:uridine 5′-phosphotransferase; uridine kinase

Systematic name:

ATP:uridine/cytidine 5′-phosphotransferase

Comments:

The enzyme, found in prokaryotes and eukaryotes, phosphorylates both uridine and cytidine to their monophosphate forms. The enzyme from Escherichia coli prefers GTP to ATP. The human enzyme also catalyses the phosphorylation of several cytotoxic ribonucleoside analogs. cf. EC 2.7.1.213, cytidine kinase.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9026-39-5

References:

1.	Sköld, O. Uridine kinase from Erlich ascites tumor: purification and properties. J. Biol. Chem. 235 (1960) 3273–3279.
2.	Orengo, A. Regulation of enzymic activity by metabolites. I. Uridine-cytidine kinase of Novikoff ascites rat tumor. J. Biol. Chem. 244 (1969) 2204–2209. [PMID: 5782006]
3.	Valentin-Hansen, P. Uridine-cytidine kinase from Escherichia coli. Methods Enzymol. 51 (1978) 308–314. [PMID: 211379]
4.	Kern, L. The URK1 gene of Saccharomyces cerevisiae encoding uridine kinase. Nucleic Acids Res. 18:5279 (1990). [PMID: 2169608]
5.	Van Rompay, A.R., Norda, A., Linden, K., Johansson, M. and Karlsson, A. Phosphorylation of uridine and cytidine nucleoside analogs by two human uridine-cytidine kinases. Mol. Pharmacol. 59 (2001) 1181–1186. [PMID: 11306702]
6.	Ohler, L., Niopek-Witz, S., Mainguet, S.E. and Mohlmann, T. Pyrimidine salvage: physiological functions and interaction with chloroplast biogenesis. Plant Physiol. 180 (2019) 1816–1828. [PMID: 31101721]

[EC 2.7.1.48 created 1965, modified 2020]

2.7.1.231

Accepted name:

3-oxoisoapionate kinase

Reaction:

ATP + 3-oxoisoapionate = ADP + 3-oxoisoapionate 4-phosphate

Glossary:

3-oxoisoapionate = 2,4-dihydroxy-2-(hydroxymethyl)-3-oxobutanoate

Other name(s):

oiaK (gene name)

Systematic name:

ATP:3-oxoisoapionate 4-phosphotransferase

Comments:

The enzyme, characterized from several bacterial species, participates in the degradation of D-apionate. Stereospecificity of the product, 3-oxoisoapionate 4-phosphate, has not been determined.

Links to other databases:

References:

Carter, M.S., Zhang, X., Huang, H., Bouvier, J.T., Francisco, B.S., Vetting, M.W., Al-Obaidi, N., Bonanno, J.B., Ghosh, A., Zallot, R.G., Andersen, H.M., Almo, S.C. and Gerlt, J.A. Functional assignment of multiple catabolic pathways for D-apiose. Nat. Chem. Biol. 14 (2018) 696–705. [DOI] [PMID: 29867142]

[EC 2.7.1.231 created 2020]

2.7.2.13

Deleted entry:

glutamate 1-kinase. Now known to be due to the activities of EC 6.1.1.17, glutamate—tRNA ligase, EC 1.2.1.70, glutamyl-tRNA reductase and EC 5.4.3.8,

[EC 2.7.2.13 created 1984, deleted 2020]

2.7.4.33

Accepted name:

AMP-polyphosphate phosphotransferase

Reaction:

ADP + (phosphate)_n = AMP + (phosphate)_n+1

Other name(s):

PA3455 (locus name); PPK2D; PAP

Systematic name:

ADP:polyphosphate phosphotransferase

Comments:

The enzyme, characterized from the bacteria Acinetobacter johnsonii and Pseudomonas aeruginosa, transfers a phosphate group from polyphosphates to nucleotide monophosphates. The highest activity is achieved with AMP, but the enzyme can also phosphorylate GMP, dAMP, dGMP, IMP, and XMP. The reverse reactions were not detected.

Links to other databases:

References:

1.	Bonting, C.F., Kortstee, G.J. and Zehnder, A.J. Properties of polyphosphate: AMP phosphotransferase of Acinetobacter strain 210A. J. Bacteriol. 173 (1991) 6484–6488. [PMID: 1655714]
2.	Shiba, T., Itoh, H., Kameda, A., Kobayashi, K., Kawazoe, Y. and Noguchi, T. Polyphosphate:AMP phosphotransferase as a polyphosphate-dependent nucleoside monophosphate kinase in Acinetobacter johnsonii 210A. J. Bacteriol. 187 (2005) 1859–1865. [PMID: 15716459]
3.	Nocek, B., Kochinyan, S., Proudfoot, M., Brown, G., Evdokimova, E., Osipiuk, J., Edwards, A.M., Savchenko, A., Joachimiak, A. and Yakunin, A.F. Polyphosphate-dependent synthesis of ATP and ADP by the family-2 polyphosphate kinases in bacteria. Proc. Natl. Acad. Sci. USA 105 (2008) 17730–17735. [PMID: 19001261]

[EC 2.7.4.33 created 2020]

*EC

2.7.7.68

Accepted name:

2-phospho-L-lactate guanylyltransferase

Reaction:

(2S)-2-phospholactate + GTP = (2S)-lactyl-2-diphospho-5′-guanosine + diphosphate

For diagram of coenzyme F₄₂₀ biosynthesis, click here

Other name(s):

cofC (gene name) (ambiguous)

Systematic name:

GTP:2-phospho-L-lactate guanylyltransferase

Comments:

This enzyme is involved in the biosynthesis of coenzyme F₄₂₀, a redox-active cofactor, in all methanogenic archaea. cf. EC 2.7.7.105, phosphoenolpyruvate guanylyltransferase and EC 2.7.7.106, 3-phospho-(R)-glycerate guanylyltransferase.

Links to other databases:

References:

1.	Grochowski, L.L., Xu, H. and White, R.H. Identification and characterization of the 2-phospho-L-lactate guanylyltransferase involved in coenzyme F₄₂₀ biosynthesis. Biochemistry 47 (2008) 3033–3037. [DOI] [PMID: 18260642]
2.	Braga, D., Last, D., Hasan, M., Guo, H., Leichnitz, D., Uzum, Z., Richter, I., Schalk, F., Beemelmanns, C., Hertweck, C. and Lackner, G. Metabolic pathway rerouting in Paraburkholderia rhizoxinica evolved long-overlooked derivatives of coenzyme F₄₂₀. ACS Chem. Biol. 14 (2019) 2088–2094. [PMID: 31469543]

[EC 2.7.7.68 created 2010, revised 2019, modified 2020]

2.7.7.104

Accepted name:

2-hydroxyethylphosphonate cytidylyltransferase

Reaction:

2-hydroxyethylphosphonate + CTP = cytidine 5′-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} + diphosphate

Other name(s):

Fom1

Systematic name:

CTP:2-hydroxyethylphosphonate cytidylyltransferase

Comments:

The enzyme, isolated from the bacterium Streptomyces wedmorensis, is involved in fosfomycin biosynthesis. The enzyme also is active as EC 5.4.2.9 phosphoenolpyruvate mutase.

Links to other databases:

References:

Cho, S.H., Kim, S.Y., Tomita, T., Shiraishi, T., Park, J.S., Sato, S., Kudo, F., Eguchi, T., Funa, N., Nishiyama, M. and Kuzuyama, T. Fosfomycin biosynthesis via transient cytidylylation of 2-hydroxyethylphosphonate by the bifunctional Fom1 enzyme. ACS Chem. Biol. 12 (2017) 2209–2215. [PMID: 28727444]

[EC 2.7.7.104 created 2020]

2.7.7.105

Accepted name:

phosphoenolpyruvate guanylyltransferase

Reaction:

phosphoenolpyruvate + GTP = enolpyruvoyl-2-diphospho-5′-guanosine + diphosphate

For diagram of coenzyme F₄₂₀ biosynthesis, click here

Other name(s):

fbiD (gene name)

Systematic name:

GTP:phosphoenolpyruvate guanylyltransferase

Comments:

This enzyme is involved in the biosynthesis of coenzyme F₄₂₀, a redox-active cofactor, in mycobacteria. cf. EC 2.7.7.68, 2-phospho-L-lactate guanylyltransferase and EC 2.7.7.106, 3-phospho-(R)-glycerate guanylyltransferase.

Links to other databases:

References:

1.	Bashiri, G., Antoney, J., Jirgis, E.NM., Shah, M.V., Ney, B., Copp, J., Stuteley, S.M., Sreebhavan, S., Palmer, B., Middleditch, M., Tokuriki, N., Greening, C., Scott, C., Baker, E.N. and Jackson, C.J. A revised biosynthetic pathway for the cofactor F₄₂₀ in prokaryotes. Nat. Commun. 10:1558 (2019). [DOI] [PMID: 30952857]
2.	Braga, D., Last, D., Hasan, M., Guo, H., Leichnitz, D., Uzum, Z., Richter, I., Schalk, F., Beemelmanns, C., Hertweck, C. and Lackner, G. Metabolic pathway rerouting in Paraburkholderia rhizoxinica evolved long-overlooked derivatives of coenzyme F₄₂₀. ACS Chem. Biol. 14 (2019) 2088–2094. [PMID: 31469543]

[EC 2.7.7.105 created 2020]

2.7.7.106

Accepted name:

3-phospho-D-glycerate guanylyltransferase

Reaction:

3-phospho-D-glycerate + GTP = 3-(D-glyceryl)-diphospho-5′-guanosine + diphosphate

Other name(s):

cofC (gene name) (ambiguous)

Systematic name:

GTP:3-phospho-D-glycerate guanylyltransferase

Comments:

The enzyme, characterized from the Gram-negative bacterium Paraburkholderia rhizoxinica, participates in the biosynthesis of 3PG-factor 420. The enzyme can also accept 2-phospho-L-lactate and phosphoenolpyruvate, but activity is much higher with 3-phospho-D-glycerate. cf. EC 2.7.7.68, 2-phospho-L-lactate guanylyltransferase and EC 2.7.7.105, phosphoenolpyruvate guanylyltransferase.

Links to other databases:

References:

Braga, D., Last, D., Hasan, M., Guo, H., Leichnitz, D., Uzum, Z., Richter, I., Schalk, F., Beemelmanns, C., Hertweck, C. and Lackner, G. Metabolic pathway rerouting in Paraburkholderia rhizoxinica evolved long-overlooked derivatives of coenzyme F₄₂₀. ACS Chem. Biol. 14 (2019) 2088–2094. [PMID: 31469543]

[EC 2.7.7.106 created 2020]

*EC

2.7.8.28

Accepted name:

2-phospho-L-lactate transferase

Reaction:

(1) (2S)-lactyl-2-diphospho-5′-guanosine + 7,8-didemethyl-8-hydroxy-5-deazariboflavin = GMP + factor 420-0
(2) enolpyruvoyl-2-diphospho-5′-guanosine + 7,8-didemethyl-8-hydroxy-5-deazariboflavin = GMP + dehydro factor 420-0
(3) 3-[(R)-glyceryl]-diphospho-5′-guanosine + 7,8-didemethyl-8-hydroxy-5-deazariboflavin = GMP + 3PG-factor 420-0

For diagram of coenzyme F₄₂₀ biosynthesis, click here

Glossary:

factor 420 = coenzyme F₄₂₀ = N-(N-{O-[5-(8-hydroxy-2,4-dioxo-2,3,4,10-tetrahydropyrimido[4,5-b]quinolin-10-yl)-5-deoxy-L-ribityl-1-phospho]-(S)-lactyl}-γ-L-glutamyl)-L-glutamate
dehydro coenzyme F₄₂₀-0 = 7,8-didemethyl-8-hydroxy-5-deazariboflavin 5′-(1-carboxyvinyl)phosphate
GMP = guanosine 5′-phosphate

Other name(s):

cofD (gene name); fbiA (gene name); LPPG:Fo 2-phospho-L-lactate transferase; LPPG:7,8-didemethyl-8-hydroxy-5-deazariboflavin 2-phospho-L-lactate transferase; lactyl-2-diphospho-(5′)guanosine:Fo 2-phospho-L-lactate transferase

Systematic name:

(2S)-lactyl-2-diphospho-5′-guanosine:7,8-didemethyl-8-hydroxy-5-deazariboflavin 2-phospho-L-lactate transferase

Comments:

This enzyme is involved in the biosynthesis of factor 420, a redox-active cofactor, in methanogenic archaea and certain bacteria. The specific reaction catalysed in vivo is determined by the availability of substrate, which in turn is determined by the enzyme present in the organism - EC 2.7.7.68, 2-phospho-L-lactate guanylyltransferase, EC 2.7.7.105, phosphoenolpyruvate guanylyltransferase, or EC 2.7.7.106, 3-phospho-D-glycerate guanylyltransferase.

Links to other databases:

References:

1.	Graupner, M., Xu, H. and White, R.H. Characterization of the 2-phospho-L-lactate transferase enzyme involved in coenzyme F₄₂₀ biosynthesis in Methanococcus jannaschii. Biochemistry 41 (2002) 3754–3761. [DOI] [PMID: 11888293]
2.	Forouhar, F., Abashidze, M., Xu, H., Grochowski, L.L., Seetharaman, J., Hussain, M., Kuzin, A., Chen, Y., Zhou, W., Xiao, R., Acton, T.B., Montelione, G.T., Galinier, A., White, R.H. and Tong, L. Molecular insights into the biosynthesis of the F₄₂₀ coenzyme. J. Biol. Chem. 283 (2008) 11832–11840. [DOI] [PMID: 18252724]
3.	Braga, D., Last, D., Hasan, M., Guo, H., Leichnitz, D., Uzum, Z., Richter, I., Schalk, F., Beemelmanns, C., Hertweck, C. and Lackner, G. Metabolic pathway rerouting in Paraburkholderia rhizoxinica evolved long-overlooked derivatives of coenzyme F₄₂₀. ACS Chem. Biol. 14 (2019) 2088–2094. [PMID: 31469543]

[EC 2.7.8.28 created 2010, modified 2020]

3.2.1.214

Accepted name:

exo β-1,2-glucooligosaccharide sophorohydrolase (non-reducing end)

Reaction:

[(1→2)-β-D-glucosyl]_n + H₂O = sophorose + [(1→2)-β-D-glucosyl]_n-2

Glossary:

sophorose = β-D-glucopyranosyl-(1→2)-D-glucopyranose

Systematic name:

exo (1→2)-β-D-glucooligosaccharide sophorohydrolase (non-reducing end)

Comments:

The enzyme, characterized from the bacterium Parabacteroides distasonis, specifically hydrolyses (1→2)-β-D-glucooligosaccharides to sophorose. The best substrates are the tetra- and pentasaccharides. The enzyme is not able to cleave the trisaccharide, and activity with longer linear (1→2)-β-D-glucans is quite low. This enzyme acts in exo mode and is not able to hydrolyse cyclic (1→2)-β-D-glucans.

Links to other databases:

References:

Shimizu, H., Nakajima, M., Miyanaga, A., Takahashi, Y., Tanaka, N., Kobayashi, K., Sugimoto, N., Nakai, H. and Taguchi, H. Characterization and structural analysis of a novel exo-type enzyme acting on β-1,2-glucooligosaccharides from Parabacteroides distasonis. Biochemistry 57 (2018) 3849–3860. [PMID: 29763309]

[EC 3.2.1.214 created 2020]

*EC

3.2.2.9

Accepted name:

adenosylhomocysteine nucleosidase

Reaction:

(1) S-adenosyl-L-homocysteine + H₂O = S-(5-deoxy-D-ribos-5-yl)-L-homocysteine + adenine
(2) 5′-deoxyadenosine + H₂O = 5-deoxy-D-ribose + adenine
(3) S-methyl-5′-thioadenosine + H₂O = 5-(methylsulfanyl)-D-ribose + adenine

For diagram of autoinducer AI-2 biosynthesis, click here and for diagram of the methionine-salvage pathway, click here

Other name(s):

S-adenosylhomocysteine hydrolase (ambiguous); S-adenosylhomocysteine nucleosidase; 5′-methyladenosine nucleosidase; S-adenosylhomocysteine/5′-methylthioadenosine nucleosidase; AdoHcy/MTA nucleosidase; MTN2 (gene name); mtnN (gene name)

Systematic name:

S-adenosyl-L-homocysteine homocysteinylribohydrolase

Comments:

This enzyme, found in bacteria and plants, acts on three different substrates. It is involved in the S-adenosyl-L-methionine (SAM, AdoMet) cycle, which recycles S-adenosyl-L-homocysteine back to SAM, and in salvage pathways for 5′-deoxyadenosine and S-methyl-5′-thioadenosine, which are produced from SAM during the action of many enzymes. cf. the plant enzyme EC 3.2.2.16, methylthioadenosine nucleosidase.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9055-10-1

References:

1.	Duerre, J.A. A hydrolytic nucleosidase acting on S-adenosylhomocysteine and on 5-methylthioadenosine. J. Biol. Chem. 237 (1962) 3737–3741.
2.	Ferro, A.J., Barrett, A. and Shapiro, S.K. Kinetic properties and the effect of substrate analogues on 5′-methylthioadenosine nucleosidase from Escherichia coli. Biochim. Biophys. Acta 438 (1976) 487–494. [DOI] [PMID: 782530]
3.	Cornell, K.A., Swarts, W.E., Barry, R.D. and Riscoe, M.K. Characterization of recombinant Eschericha coli 5′-methylthioadenosine/S-adenosylhomocysteine nucleosidase: analysis of enzymatic activity and substrate specificity. Biochem. Biophys. Res. Commun. 228 (1996) 724–732. [PMID: 8941345]
4.	Park, E.Y., Choi, W.S., Oh, S.I., Kim, K.N., Shin, J.S. and Song, H.K. Biochemical and structural characterization of 5′-methylthioadenosine nucleosidases from Arabidopsis thaliana. Biochem. Biophys. Res. Commun. 381 (2009) 619–624. [PMID: 19249293]
5.	Farrar, C.E., Siu, K.K., Howell, P.L. and Jarrett, J.T. Biotin synthase exhibits burst kinetics and multiple turnovers in the absence of inhibition by products and product-related biomolecules. Biochemistry 49 (2010) 9985–9996. [PMID: 20961145]
6.	North, J.A., Wildenthal, J.A., Erb, T.J., Evans, B.S., Byerly, K.M., Gerlt, J.A. and Tabita, F.R. A bifunctional salvage pathway for two distinct S-adenosylmethionine by-products that is widespread in bacteria, including pathogenic Escherichia coli. Mol. Microbiol. (2020) . [PMID: 31950558]

[EC 3.2.2.9 created 1972, modified 2004, modified 2020]

*EC

3.5.1.110

Accepted name:

ureidoacrylate amidohydrolase

Reaction:

(1) (Z)-3-ureidoacrylate + H₂O = (Z)-3-aminoacrylate + CO₂ + NH₃ (overall reaction)
(1a) (Z)-3-ureidoacrylate + H₂O = (Z)-3-aminoacrylate + carbamate
(1b) carbamate = CO₂ + NH₃ (spontaneous)
(2) (Z)-2-methylureidoacrylate + H₂O = (Z)-2-methylaminoacrylate + CO₂ + NH₃ (overall reaction)
(2a) (Z)-2-methylureidoacrylate + H₂O = (Z)-2-methylaminoacrylate + carbamate
(2b) carbamate = CO₂ + NH₃ (spontaneous)

For diagram of pyrimidine catabolism, click here

Glossary:

(Z)-3-ureidoacrylate = (2Z)-3-(carbamoylamino)prop-2-enoate
(Z)-2-methylureidoacrylate = (2Z)-3-(carbamoylamino)-2-methylprop-2-enoate

Other name(s):

peroxyureidoacrylate/ureidoacrylate amidohydrolase; rutB (gene name); (Z)-3-ureidoacrylate peracid amidohydrolase

Systematic name:

(Z)-3-ureidoacrylate amidohydrolase

Comments:

The enzyme participates in the Rut pyrimidine catabolic pathway.

Links to other databases:

References:

1.	Kim, K.S., Pelton, J.G., Inwood, W.B., Andersen, U., Kustu, S. and Wemmer, D.E. The Rut pathway for pyrimidine degradation: novel chemistry and toxicity problems. J. Bacteriol. 192 (2010) 4089–4102. [DOI] [PMID: 20400551]

[EC 3.5.1.110 created 2012, modified 2020]

3.5.1.135

Accepted name:

N⁴-acetylcytidine amidohydrolase

Reaction:

N⁴-acetylcytidine + H₂O = cytidine + acetate

Other name(s):

yqfB (gene name)

Systematic name:

N⁴-acetylcytidine amidohydrolase

Comments:

The enzyme from the bacterium Escherichia coli is one of the smallest known monomeric amidohydrolases (103-amino acids). The enzyme is active towards a wide range of N⁴-acylcytosines/cytidines, but is by far most active against N⁴-acetylcytidine.

Links to other databases:

References:

1.	Shen, Y., Atreya, H.S., Liu, G. and Szyperski, T. G-matrix Fourier transform NOESY-based protocol for high-quality protein structure determination. J. Am. Chem. Soc. 127 (2005) 9085–9099. [PMID: 15969587]
2.	Stanislauskiene, R., Laurynenas, A., Rutkiene, R., Aucynaite, A., Tauraite, D., Meskiene, R., Urbeliene, N., Kaupinis, A., Valius, M., Kaliniene, L. and Meskys, R. YqfB protein from Escherichia coli: an atypical amidohydrolase active towards N⁴-acylcytosine derivatives. Sci. Rep. 10:788 (2020). [PMID: 31964920]

[EC 3.5.1.135 created 2020]

3.6.1.3

Deleted entry:

adenosinetriphosphatase. Enzymes previously listed under this number are now listed separately under EC 5.6 and EC 7.

[EC 3.6.1.3 created 1961 (EC 3.6.1.4 created 1961, incorporated 1965), deleted 2020]

3.6.3.11

Deleted entry:

Cl^--transporting ATPase. The activity was only ever studied in crude extracts, and is an artifact.

[EC 3.6.3.11 created 2000, deleted 2020]

3.8.1.1

Deleted entry:

alkylhalidase. Covered by EC 3.8.1.5, haloalkane dehalogenase.

[EC 3.8.1.1 created 1961, deleted 2020]

4.1.1.120

Accepted name:

3-oxoisoapionate decarboxylase

Reaction:

3-oxoisoapionate = L-erythrulose + CO₂

Glossary:

3-oxoisoapionate = 2,4-dihydroxy-2-(hydroxymethyl)-3-oxobutanoate

Other name(s):

oiaC (gene name)

Systematic name:

3-oxoisoapionate carboxy-lyase

Comments:

The enzyme, characterized from several bacterial species, is involved in the degradation of D-apionate. Stereospecificity of 3-oxoisoapionate has not been determined.

Links to other databases:

References:

[EC 4.1.1.120 created 2020]

4.1.1.121

Accepted name:

3-oxoisoapionate-4-phosphate decarboxylase

Reaction:

3-oxoisoapionate 4-phosphate = L-erythrulose 1-phosphate + CO₂

Glossary:

3-oxoisoapionate = 2,4-dihydroxy-2-(hydroxymethyl)-3-oxobutanoate

Other name(s):

oiaX (gene name)

Systematic name:

3-oxoisoapionate 4-phosphate carboxy-lyase

Comments:

The enzyme, characterized from several bacterial species, participates in the degradation of D-apionate. It belongs to the RuBisCO-like-protein (RLP) superfamily. Stereospecificity of 3-oxoisoapionate 4-phosphate has not been determined.

Links to other databases:

References:

[EC 4.1.1.121 created 2020]

4.1.2.62

Accepted name:

5-deoxyribulose 1-phosphate aldolase

Reaction:

(1) 5-deoxy-D-ribulose 1-phosphate = glycerone phosphate + acetaldehyde
(2) S-methyl-5-thio-D-ribulose 1-phosphate = glycerone phosphate + (2-methylsulfanyl)acetaldehyde

Other name(s):

5-(methylthio)ribulose-1-phosphate aldolase; ald2 (gene name)

Systematic name:

5-deoxy-D-ribulose 1-phosphate acetaldehyde-lyase (glycerone-phosphate-forming)

Comments:

The enzyme, originally characterized from the bacterium Rhodospirillum rubrum, is involved in degradation pathways for 5′-deoxyadenosine and S-methyl-5′-thioadenosine, which are formed from S-adenosyl-L-methionine (SAM, AdoMet) by radical SAM enzymes and other types of SAM-dependent enzymes, respectively. The enzyme requires a divalent metal cation, with Co²⁺ producing the highest activity.

Links to other databases:

References:

1.	North, J.A., Miller, A.R., Wildenthal, J.A., Young, S.J. and Tabita, F.R. Microbial pathway for anaerobic 5′-methylthioadenosine metabolism coupled to ethylene formation. Proc. Natl. Acad. Sci. USA 114 (2017) E10455–E10464. [PMID: 29133429]
2.	North, J.A., Wildenthal, J.A., Erb, T.J., Evans, B.S., Byerly, K.M., Gerlt, J.A. and Tabita, F.R. A bifunctional salvage pathway for two distinct S-adenosylmethionine by-products that is widespread in bacteria, including pathogenic Escherichia coli. Mol. Microbiol. (2020) . [PMID: 31950558]

[EC 4.1.2.62 created 2020]

*EC

4.99.1.3

Accepted name:

sirohydrochlorin cobaltochelatase

Reaction:

cobalt-sirohydrochlorin + 2 H⁺ = sirohydrochlorin + Co²⁺

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

Other name(s):

CbiK; CbiX; CbiXS; anaerobic cobalt chelatase; cobaltochelatase [ambiguous]; sirohydrochlorin cobalt-lyase

Systematic name:

cobalt-sirohydrochlorin cobalt-lyase (sirohydrochlorin-forming)

Comments:

This enzyme, which forms part of the anaerobic (early cobalt insertion) cobalamin biosynthesis pathway, is an ATP-independent type II chelatase. Two distinct forms are known - a primordial form named CbiX, which is most common in archaea, and a strictly bacterial form named CbiK. See EC 6.6.1.2, cobaltochelatase, for the cobaltochelatase that participates in the aerobic cobalamin biosynthesis pathway.

Links to other databases:

References:

1.	Raux, E., Thermes, C., Heathcote, P., Rambach, A. and Warren, M.J. A role for Salmonella typhimurium cbiK in cobalamin (vitamin B₁₂) and siroheme biosynthesis. J. Bacteriol. 179 (1997) 3202–3212. [DOI] [PMID: 9150215]
2.	Schubert, H.L., Raux, E., Wilson, K.S. and Warren, M.J. Common chelatase design in the branched tetrapyrrole pathways of heme and anaerobic cobalamin synthesis. Biochemistry 38 (1999) 10660–10669. [DOI] [PMID: 10451360]
3.	Warren, M.J., Raux, E., Schubert, H.L. and Escalante-Semerena, J.C. The biosynthesis of adenosylcobalamin (vitamin B₁₂). Nat. Prod. Rep. 19 (2002) 390–412. [PMID: 12195810]
4.	Brindley, A.A., Raux, E., Leech, H.K., Schubert, H.L. and Warren, M.J. A story of chelatase evolution: Identification and characterisation of a small 13-15 kDa 'ancestral' cobaltochelatase (CbiXS) in the Archaea. J. Biol. Chem. 278 (2003) 22388–22395. [DOI] [PMID: 12686546]
5.	Frank, S., Brindley, A.A., Deery, E., Heathcote, P., Lawrence, A.D., Leech, H.K., Pickersgill, R.W. and Warren, M.J. Anaerobic synthesis of vitamin B₁₂: characterization of the early steps in the pathway. Biochem Soc Trans. 33 (2005) 811–814. [DOI] [PMID: 16042604]
6.	Lobo, S.A., Brindley, A.A., Romao, C.V., Leech, H.K., Warren, M.J. and Saraiva, L.M. Two distinct roles for two functional cobaltochelatases (CbiK) in Desulfovibrio vulgaris hildenborough. Biochemistry 47 (2008) 5851–5857. [DOI] [PMID: 18457416]
7.	Lobo, S.A., Videira, M.A., Pacheco, I., Wass, M.N., Warren, M.J., Teixeira, M., Matias, P.M., Romao, C.V. and Saraiva, L.M. Desulfovibrio vulgaris CbiK(P) cobaltochelatase: evolution of a haem binding protein orchestrated by the incorporation of two histidine residues. Environ. Microbiol. 19 (2017) 106–118. [DOI] [PMID: 27486032]

[EC 4.99.1.3 created 2004, modified 2020]

5.1.3.12

Deleted entry:

UDP-glucuronate 5-epimerase. The enzyme has never been purified and the activity was later shown not to exist.

[EC 5.1.3.12 created 1972, deleted 2020]

*EC

5.1.3.18

Accepted name:

GDP-mannose 3,5-epimerase

Reaction:

(1) GDP-α-D-mannose = GDP-β-L-galactose
(2) GDP-α-D-mannose = GDP-β-L-gulose

Other name(s):

GME (gene name); GDP-D-mannose:GDP-L-galactose epimerase; guanosine 5′-diphosphate D-mannose:guanosine 5′-diphosphate L-galactose epimerase

Systematic name:

GDP-α-D-mannose 3,5-epimerase

Comments:

The enzyme catalyses the formation of the stable intermediate GDP-β-L-gulose as well as GDP-β-L-galactose. The reaction proceeds by C4′ oxidation of GDP-α-D-mannose followed by epimerization of the C5′ position to give GDP-β-L-4-dehydro-gulose. This intermediate is either reduced to give GDP-β-L-gulose or the C3′ position is epimerized to give GDP-β-L-4-dehydro-galactose, followed by C4′ reduction to yield GDP-β-L-galactose. Both products serve as intermediates in two different variants of plant L-ascorbate biosynthesis pathways.

Links to other databases:

BRENDA, EXPASY, Gene, GTD, KEGG, PDB, CAS registry number: 72162-82-4

References:

1.	Hebda, P.A., Behrman, E.J. and Barber, G.A. The guanosine 5′-diphosphate D-mannose: guanosine 5′-diphosphate L-galactose epimerase of Chlorella pyrenoidosa. Chemical synthesis of guanosine 5′-diphosphate L-galactose and further studies of the enzyme and the reaction it catalyzes. Arch. Biochem. Biophys. 194 (1979) 496–502. [DOI] [PMID: 443816]
2.	Barber, G.A. and Hebda, P.A. GDP-D-mannose: GDP-L-galactose epimerase from Chlorella pyrenoidosa. Methods Enzymol. 83 (1982) 522–525. [PMID: 7098948]
3.	Wolucka, B.A., Persiau, G., Van Doorsselaere, J., Davey, M.W., Demol, H., Vandekerckhove, J., Van Montagu, M., Zabeau, M. and Boerjan, W. Partial purification and identification of GDP-mannose 3",5"-epimerase of Arabidopsis thaliana, a key enzyme of the plant vitamin C pathway. Proc. Natl. Acad. Sci. USA 98 (2001) 14843–14848. [PMID: 11752432]
4.	Major, L.L., Wolucka, B.A. and Naismith, J.H. Structure and function of GDP-mannose-3′,5′-epimerase: an enzyme which performs three chemical reactions at the same active site. J. Am. Chem. Soc. 127 (2005) 18309–18320. [PMID: 16366586]
5.	Watanabe, K., Suzuki, K. and Kitamura, S. Characterization of a GDP-D-mannose 3′′,5′′-epimerase from rice. Phytochemistry 67 (2006) 338–346. [PMID: 16413588]

[EC 5.1.3.18 created 1986, modified 2020]

6.2.1.64

Accepted name:

E1 NEDD8-activating enzyme

Reaction:

ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine = AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine

Glossary:

NEDD = Neural-precursor-cell Expressed Developmentally Down-regulated protein

Other name(s):

NEDD-activating enzyme E1; NAE1 (gene name); UBA3 (gene name)

Systematic name:

[NEDD8 protein]:[E1 NEDD8-activating enzyme] ligase (AMP-forming)

Comments:

Some RING-type E3 ubiquitin transferase (EC 2.3.2.27) are not able to bind a substrate protein directly. Instead, they form complexes with a cullin scaffold protein and a substrate recognition module, which are known as CRL (Cullin-RING-Ligase) complexes. The cullin protein needs to be activated by the ubiquitin-like protein NEDD8 in a process known as neddylation. Like ubiquitin, the NEDD8 protein ends with two glycine residues. The E1 NEDD8-activating enzyme activates NEDD8 in an ATP-dependent reaction by forming a high-energy thioester intermediate between NEDD8 and one of its cysteine residues. The activated NEDD8 is subsequently transferred to a cysteine residue of EC 2.3.2.34, E2 NEDD8-conjugating enzyme, and is eventually conjugated to a lysine residue of specific substrates in the presence of the appropriate E3 transferase (EC 2.3.2.32, cullin-RING-type E3 NEDD8 transferase).

Links to other databases:

References:

1.	Osaka, F., Kawasaki, H., Aida, N., Saeki, M., Chiba, T., Kawashima, S., Tanaka, K. and Kato, S. A new NEDD8-ligating system for cullin-4A. Genes Dev. 12 (1998) 2263–2268. [PMID: 9694792]
2.	Gong, L. and Yeh, E.T. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J. Biol. Chem. 274 (1999) 12036–12042. [PMID: 10207026]

[EC 6.2.1.64 created 2020]

6.2.1.65

Accepted name:

salicylate—CoA ligase

Reaction:

ATP + salicylate + CoA = AMP + diphosphate + 2-hydroxybenzoyl-CoA (overall reaction)
(1a) ATP + salicylate = diphosphate + (2-hydroxybenzoyl)adenylate
(1b) (2-hydroxybenzoyl)adenylate + CoA = AMP + 2-hydroxybenzoyl-CoA

Glossary:

2-hydroxybenzoyl-CoA = salicyloyl-CoA

Other name(s):

sdgA (gene name)

Systematic name:

salicylate:CoA ligase (AMP-forming)

Comments:

The enzyme, characterized from the bacteria Thauera aromatica and Streptomyces sp. WA46, participates in a salicylate degradation pathway. It activates salicylate by its adenylation to (2-hydroxybenzoyl)adenylate, followed by the transfer of the activated compound to coenzyme A.

Links to other databases:

References:

1.	Bonting, C.F. and Fuchs, G. Anaerobic metabolism of 2-hydroxybenzoic acid (salicylic acid) by a denitrifying bacterium. Arch. Microbiol. 165 (1996) 402–408. [PMID: 8661934]
2.	Ishiyama, D., Vujaklija, D. and Davies, J. Novel pathway of salicylate degradation by Streptomyces sp. strain WA46. Appl. Environ. Microbiol. 70 (2004) 1297–1306. [DOI] [PMID: 15006746]

[EC 6.2.1.65 created 2020]

6.2 Forming carbon-sulfur bonds

6.2.2 Amide—thiol ligases

6.2.2.1

Accepted name:

thioglycine synthase

Reaction:

ATP + sulfide + a [methyl-coenzyme M reductase]-glycine = ADP + phosphate + a [methyl-coenzyme M reductase]-thioglycine

Glossary:

thioglycine = 2-aminoethanethioic O-acid

Other name(s):

ycaO (gene name) (ambiguous)

Systematic name:

[methyl-coenzyme M reductase]-glycine—sulfur ligase (thioglycine-forming)

Comments:

Requires Mg²⁺. The enzyme is found in anaerobic methanogenic and methanotrophic archaea, where it modifies a glycine residue in EC 2.8.4.1, coenzyme-B sulfoethylthiotransferase (methyl-CoM reductase). Upon binding to its substrate, an external source of sulfide attacks the target amide bond generating a tetrahedral intermediate. The amide oxyanion attacks the γ-phosphate of ATP, releasing ADP and forming a phosphorylated thiolate intermediate that collapses to form thioglycine and phosphate. In most organisms activity requires a second protein (TfuA) , which may allosterically activate this enzyme or assist in the delivery of sulfide to the substrate.

Links to other databases:

References:

1.	Nayak, D.D., Mahanta, N., Mitchell, D.A. and Metcalf, W.W. Post-translational thioamidation of methyl-coenzyme M reductase, a key enzyme in methanogenic and methanotrophic Archaea. Elife 6:e29218 (2017). [PMID: 28880150]
2.	Mahanta, N., Liu, A., Dong, S., Nair, S.K. and Mitchell, D.A. Enzymatic reconstitution of ribosomal peptide backbone thioamidation. Proc. Natl. Acad. Sci. USA 115 (2018) 3030–3035. [PMID: 29507203]
3.	Dong, S.H., Liu, A., Mahanta, N., Mitchell, D.A. and Nair, S.K. Mechanistic basis for ribosomal peptide backbone modifications. ACS Cent. Sci. 5 (2019) 842–851. [PMID: 31139720]

[EC 6.2.2.1 created 2020]

6.2.2.2

Accepted name:

oxazoline synthase

Reaction:

(1) ATP + a [protein]-(L-amino acyl-L-serine) = ADP + phosphate + a [protein]-(S,S)-2-(C-substituted-aminomethyl)-4-acyl-2-oxazoline
(2) ATP + a [protein]-(L-amino acyl-L-threonine) = ADP + phosphate + a [protein]-(S,S)-2-(C-substituted-aminomethyl)-4-acyl-5-methyl-2-oxazoline
(3) ATP + a [protein]-(L-amino acyl-L-cysteine) = ADP + phosphate + a [protein]-(1S,4R)-2-(C-substituted-aminomethyl)-4-acyl-2-thiazoline

Other name(s):

cyanobactin heterocyclase; cyanobactin cyclodehydratase; patD (gene name); balhD (gene name); micD (gene name)

Systematic name:

[protein]-(L-amino acyl-L-serine) cyclodehydratase (2-oxazoline-forming)

Comments:

Requires Mg²⁺. The enzyme, which participates in the biosynthesis of ribosomal peptide natural products (RiPPs), converts L-cysteine, L-serine and L-threonine residues to thiazoline, oxazoline, and methyloxazoline rings, respectively. The enzyme requires two domains - a cyclodehydratase domain, known as a YcaO domain, and a substrate recognition domain (RRE domain) that controls the regiospecificity of the enzyme. The RRE domain can either be fused to the YcaO domain or occur as a separate protein; however both domains are required for activity. The enzyme can process multiple residues within the same substrate peptide, and all enzymes characterized so far follow a defined order, starting with the L-cysteine closest to the C-terminus. The reaction involves phosphorylation of the preceding ribosomal peptide backbone amide bond, forming ADP and a phosphorylated intermediate, followed by release of the phosphate group. In some cases the enzyme catalyses a side reaction in which the phosphorylated intermediate reacts with ADP to form AMP and diphosphate.

Links to other databases:

References:

1.	McIntosh, J.A., Donia, M.S. and Schmidt, E.W. Insights into heterocyclization from two highly similar enzymes. J. Am. Chem. Soc. 132 (2010) 4089–4091. [PMID: 20210311]
2.	Melby, J.O., Dunbar, K.L., Trinh, N.Q. and Mitchell, D.A. Selectivity, directionality, and promiscuity in peptide processing from a Bacillus sp. Al Hakam cyclodehydratase. J. Am. Chem. Soc. 134 (2012) 5309–5316. [PMID: 22401305]
3.	Ge, Y., Czekster, C.M., Miller, O.K., Botting, C.H., Schwarz-Linek, U. and Naismith, J.H. Insights into the mechanism of the cyanobactin heterocyclase enzyme. Biochemistry 58 (2019) 2125–2132. [PMID: 30912640]

[EC 6.2.2.2 created 2020]

6.2.2.3

Accepted name:

thiazoline synthase

Reaction:

ATP + a [protein]-(L-amino acyl-L-cysteine) = ADP + phosphate + a [protein]-(1S,4R)-2-(C-substituted-aminomethyl)-4-acyl-2-thiazoline

Glossary:

L-cysteine heterocyclase; truD (gene name); lynD (gene name)

Systematic name:

[protein]-(L-amino acyl-L-cysteine) cyclodehydratase (2-thiazoline-forming)

Comments:

Requires Mg²⁺. The enzyme, which participates in the biosynthesis of some ribosomal peptide natural products (RiPPs) such as the trunkamides, converts L-cysteine residues to thiazoline rings. The enzyme requires two domains - a cyclodehydratase domain, known as a YcaO domain, and a substrate recognition domain (RRE domain) that controls the regiospecificity of the enzyme. The RRE domain can either be fused to the YcaO domain or occur as a separate protein; however both domains are required for activity. The enzyme can process multiple L-cysteine residues within the same substrate peptide, and all enzymes characterized so far follow a defined order, starting with the L-cysteine closest to the C-terminus. The reaction involves phosphorylation of the preceding ribosomal peptide backbone amide bond, forming ADP and a phosphorylated intermediate, followed by release of the phosphate group. In some cases the enzyme catalyses a side reaction in which the phosphorylated intermediate reacts with ADP to form AMP and diphosphate. This activity is also catalysed by the related enzyme EC 6.2.2.2, oxazoline synthase. That enzyme differs by having an RRE domain that also recognizes L-serine and L-threonine residues, which are converted to oxazoline and methyloxazoline rings, respectively.

Links to other databases:

References:

1.	McIntosh, J.A. and Schmidt, E.W. Marine molecular machines: heterocyclization in cyanobactin biosynthesis. ChemBioChem 11 (2010) 1413–1421. [PMID: 20540059]
2.	McIntosh, J.A., Donia, M.S. and Schmidt, E.W. Insights into heterocyclization from two highly similar enzymes. J. Am. Chem. Soc. 132 (2010) 4089–4091. [PMID: 20210311]
3.	Koehnke, J., Bent, A.F., Zollman, D., Smith, K., Houssen, W.E., Zhu, X., Mann, G., Lebl, T., Scharff, R., Shirran, S., Botting, C.H., Jaspars, M., Schwarz-Linek, U. and Naismith, J.H. The cyanobactin heterocyclase enzyme: a processive adenylase that operates with a defined order of reaction. Angew. Chem. Int. Ed. Engl. 52 (2013) 13991–13996. [PMID: 24214017]
4.	Koehnke, J., Mann, G., Bent, A.F., Ludewig, H., Shirran, S., Botting, C., Lebl, T., Houssen, W., Jaspars, M. and Naismith, J.H. Structural analysis of leader peptide binding enables leader-free cyanobactin processing. Nat. Chem. Biol. 11 (2015) 558–563. [PMID: 26098679]
5.	Ge, Y., Czekster, C.M., Miller, O.K., Botting, C.H., Schwarz-Linek, U. and Naismith, J.H. Insights into the mechanism of the cyanobactin heterocyclase enzyme. Biochemistry 58 (2019) 2125–2132. [PMID: 30912640]

[EC 6.2.2.3 created 2020]

6.5.1.9

Accepted name:

cyclic 2,3-diphosphoglycerate synthase

Reaction:

ATP + 2,3-diphospho-D-glycerate = ADP + phosphate + cyclic 2,3-bisphosphoglycerate

Other name(s):

cpgS (gene name)

Systematic name:

(2R)-2,3-bisphosphoglycerate ligase (cyclizing)

Comments:

The enzyme is present in a number of methanogenic archaeal genera that accumulate cyclic 2,3-bisphosphoglycerate as a thermoprotectant. Activity is stimulated by potassium ions.

Links to other databases: