An asterisk before "EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.
Accepted name: D-xylose 1-dehydrogenase (NADP+, D-xylono-1,5-lactone-forming)
Reaction: D-xylose + NADP+ = D-xylono-1,5-lactone + NADPH + H+
Other name(s): D-xylose (nicotinamide adenine dinucleotide phosphate) dehydrogenase (ambiguous); D-xylose-NADP dehydrogenase (ambiguous); D-xylose:NADP+ oxidoreductase (ambiguous); D-xylose 1-dehydrogenase (NADP) (ambiguous)
Systematic name: D-xylose:NADP+ 1-oxidoreductase (D-xylono-1,5-lactone-forming)
Comments: The enzyme, characterized from pig arterial vessels and eye lens, also acts, more slowly, on L-arabinose and D-ribose. cf. EC 1.1.1.424, D-xylose 1-dehydrogenase (NADP+, D-xylono-1,4-lactone-forming).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 83534-37-6
References:
1. Wissler, J.H. D-Xylose:NADP oxidoreductase of arterial vessels and eye lens: a new enzyme and a final link in ATP-independent cycling of reducing eqivalents in aldose-polyol-ketose interconversion. Hoppe-Seyler's Z. Physiol. Chem. 358 (1977) 1300-1301.
2. Wissler, J.H. Direct spectrophotometric and specific quantitative determination of free and bound D-xylose by analytical application of a new enzyme, D-xylose:NADP-oxidoreductase. Fresenius' Z. Anal. Chem. 290 (1978) 179-180.
Accepted name: (1R,2S)-ephedrine 1-dehydrogenase
Reaction: (–)-(1R,2S)-ephedrine + NAD+ = (S)-2-(methylamino)-1-phenylpropan-1-one + NADH + H+
Glossary: (–)-(1R,2S)-ephedrine = (1R,2S)-2-(methylamino)-1-phenylpropan-1-ol
(S)-2-(methylamino)-1-phenylpropan-1-one = (S)-methcathinone
Other name(s): EDH; ephedrine dehydrogenase
Systematic name: (–)-(1R,2S)-ephedrine:NAD+ 1-oxidoreductase
Comments: The enzyme, characterized from the bacterium Arthrobacter sp. TS-15, acts on a broad range of different aryl-alkyl ketones, such as haloketones, ketoamines, diketones, and ketoesters. It exhibits a strict enantioselectivity and accepts various types of aryl groups including phenyl-, pyridyl-, thienyl-, and furyl-rings, but the presence of an aromatic ring is essential for the activity. In addition, the presence of a functional group on the alkyl chain, such as an amine, a halogen, or a ketone, is also crucial. When acting on diketones, it catalyses the reduction of only the keto group closest to the ring, with no further reduction to the diol. cf. EC 1.1.1.422, pseudoephedrine dehydrogenase and EC 1.5.1.18, ephedrine dehydrogenase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
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.
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).
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. [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 1.2.2.4 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)]
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.
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]
Accepted name: protoporphyrinogen IX dehydrogenase (quinone)
Reaction: protoporphyrinogen IX + 3 quinone = protoporphyrin IX + 3 quinol
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: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
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. [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]
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.
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 (2018) 1180. [PMID: 29563586]
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.
References:
1. 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]
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.
References:
1. 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 1.14.13.116 Transferred entry: geranylhydroquinone 3-hydroxylase. Now EC 1.14.14.174, geranylhydroquinone 3-hydroxylase. (EC 1.14.13.116 created 2010, deleted 2019)]
[EC 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)]
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.
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. [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]
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,[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.
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. [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. [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 (2015) e0124106. [PMID: 26020634]
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 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.
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. [PMID: 8807878]
[EC 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)]
Accepted name: (+)-pinoresinol hydroxylase
Reaction: (+)-pinoresinol + 2 oxidized azurin + H2O = (+)-6-hydroxypinoresinol + 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.
References:
1. 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]
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: BRENDA, EXPASY, KEGG, MetaCyc CAS registry number:
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 (2010) e8570. [PMID: 20084102]
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: BRENDA, EXPASY, KEGG, MetaCyc CAS registry number:
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 2.1.1.358 Deleted entry: [histone H3]-dimethyl-L-lysine36 N-methyltransferase. Now known to have the activity of EC 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)]
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.
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]
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.
References:
1. 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 2.1.1.368 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.
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]
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.
References:
1. 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]
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.
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]
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 EC2.1.1.370, [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.
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]
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.
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]
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: BRENDA, EXPASY, KEGG, MetaCyc CAS registry number:
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. [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]
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.
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 (2019) 1558. [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]
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.
References:
1. 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]
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: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
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. [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. [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 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)]
Accepted name: salicylate—CoA ligase
Reaction: ATP + salicylate + CoA = AMP + diphosphate + salicyl-CoA (overall reaction)
(1a) ATP + salicylate = diphosphate + (salicyl)adenylate
(1b) (salicyl)adenylate + CoA = AMP + salicyl-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 (salicyl)adenylate, followed by the transfer of the activated compound to coenzyme A.
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. [PMID: 15006746]
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: [peptide]-(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.
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]
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: [peptide]-(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.
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]