Proposed Changes to the Enzyme List

References:

1.	Verduyn, C., Van Kleef, R., Frank, J., Schreuder, H., Van Dijken, J.P. and Scheffers, W.A. Properties of the NAD(P)H-dependent xylose reductase from the xylose-fermenting yeast Pichia stipitis. Biochem. J. 226 (1985) 669–677. [DOI] [PMID: 3921014]
2.	Neuhauser, W., Haltrich, D., Kulbe, K.D. and Nidetzky, B. NAD(P)H-dependent aldose reductase from the xylose-assimilating yeast Candida tenuis. Isolation, characterization and biochemical properties of the enzyme. Biochem. J. 326 (1997) 683–692. [DOI] [PMID: 9307017]
3.	Hacker, B., Habenicht, A., Kiess, M. and Mattes, R. Xylose utilisation: cloning and characterisation of the xylose reductase from Candida tenuis. Biol. Chem. 380 (1999) 1395–1403. [DOI] [PMID: 10661866]
4.	Hakulinen, N., Turunen, O., Janis, J., Leisola, M. and Rouvinen, J. Three-dimensional structures of thermophilic β-1,4-xylanases from Chaetomium thermophilum and Nonomuraea flexuosa. Comparison of twelve xylanases in relation to their thermal stability. Eur. J. Biochem. 270 (2003) 1399–1412. [DOI] [PMID: 12653995]
5.	Woodyer, R., Simurdiak, M., van der Donk, W.A. and Zhao, H. Heterologous expression, purification, and characterization of a highly active xylose reductase from Neurospora crassa. Appl. Environ. Microbiol. 71 (2005) 1642–1647. [DOI] [PMID: 15746370]
6.	Fernandes, S., Tuohy, M.G. and Murray, P.G. Xylose reductase from the thermophilic fungus Talaromyces emersonii: cloning and heterologous expression of the native gene (Texr) and a double mutant (TexrK271R + N273D) with altered coenzyme specificity. J. Biosci. 34 (2009) 881–890. [DOI] [PMID: 20093741]
7.	Quehenberger, J., Reichenbach, T., Baumann, N., Rettenbacher, L., Divne, C. and Spadiut, O. Kinetics and predicted structure of a novel xylose reductase from Chaetomium thermophilum. Int. J. Mol. Sci. 20 (2019) . [DOI] [PMID: 30621365]

[EC 1.1.1.307 created 2010, modified 2022]

*EC

1.1.1.313

Accepted name:

sulfoacetaldehyde reductase (NADPH)

Reaction:

isethionate + NADP⁺ = 2-sulfoacetaldehyde + NADPH + H⁺

Glossary:

isethionate = 2-hydroxyethanesulfonate
2-sulfoacetaldehyde = 2-oxoethanesulfonate

Other name(s):

isfD (gene name)

Systematic name:

isethionate:NADP⁺ oxidoreductase

Comments:

Catalyses the reaction only in the opposite direction. Involved in taurine degradation. The bacterium Chromohalobacter salexigens strain DSM 3043 possesses two enzymes that catalyse this reaction, a constitutive enzyme (encoded by isfD2) and an inducible enzyme (encoded by isfD). The latter is induced by taurine, and is responsible for most of the activity observed in taurine-grown cells. cf. EC 1.1.1.433, sulfoacetaldehyde reductase (NADH).

Links to other databases:

References:

1.	Krejcik, Z., Hollemeyer, K., Smits, T.H. and Cook, A.M. Isethionate formation from taurine in Chromohalobacter salexigens: purification of sulfoacetaldehyde reductase. Microbiology 156 (2010) 1547–1555. [DOI] [PMID: 20133363]

[EC 1.1.1.313 created 2011, modified 2022]

1.1.1.430

Accepted name:

D-xylose reductase (NADH)

Reaction:

xylitol + NAD⁺ = D-xylose + NADH + H⁺

Other name(s):

XYL1 (gene name) (ambiguous)

Systematic name:

xylitol:NAD⁺ oxidoreductase

Comments:

Xylose reductases catalyse the reduction of xylose to xylitol, the initial reaction in the fungal D-xylose degradation pathway. Most of the enzymes exhibit a strict requirement for NADPH (cf. EC 1.1.1.431, D-xylose reductase (NADPH)). Some D-xylose reductases have dual cosubstrate specificity, though they still prefer NADPH to NADH (cf. EC 1.1.1.307, D-xylose reductase [NAD(P)H]). The enzyme from Candida parapsilosis is a rare example of a xylose reductase that significantly prefers NADH, with K_m and V_max values for NADH being 10-fold lower and 10-fold higher, respectively, than for NADPH.

Links to other databases:

References:

1.	Lee, J.K., Koo, B.S. and Kim, S.Y. Cloning and characterization of the xyl1 gene, encoding an NADH-preferring xylose reductase from Candida parapsilosis, and its functional expression in Candida tropicalis. Appl. Environ. Microbiol. 69 (2003) 6179–6188. [DOI] [PMID: 14532079]

[EC 1.1.1.430 created 2022]

1.1.1.431

Accepted name:

D-xylose reductase (NADPH)

Reaction:

xylitol + NADP⁺ = D-xylose + NADPH + H⁺

Other name(s):

XYL1 (gene name, ambiguous); xyl1 (gene name, ambiguous); xyrA (gene name); xyrB (gene name)

Systematic name:

xylitol:NADP⁺ oxidoreductase

Comments:

Xylose reductases catalyse the reduction of xylose to xylitol, the initial reaction in the fungal D-xylose degradation pathway. Most of the enzymes exhibit a strict requirement for NADPH (e.g. the enzymes from Saccharomyces cerevisiae, Aspergillus niger, Trichoderma reesei, Candida tropicalis, Saitozyma flava, and Candida intermedia). Some D-xylose reductases have dual cosubstrate specificity, though they still prefer NADPH to NADH (cf. EC 1.1.1.307, D-xylose reductase [NAD(P)H]). Very rarely the enzyme prefers NADH (cf. EC 1.1.1.430, D-xylose reductase (NADH)).

Links to other databases:

References:

1.	Bolen, P.L. and Detroy, R.W. Induction of NADPH-linked D-xylose reductase and NAD-linked xylitol dehydrogenase activities in Pachysolen tannophilus by D-xylose, L-arabinose, or D-galactose. Biotechnol. Bioeng. 27 (1985) 302–307. [DOI] [PMID: 18553673]
2.	Suzuki, T., Yokoyama, S., Kinoshita, Y., Yamada, H., Hatsu, M., Takamizawa, K. and Kawai, K. Expression of xyrA gene encoding for D-xylose reductase of Candida tropicalis and production of xylitol in Escherichia coli. J. Biosci. Bioeng. 87 (1999) 280–284. [DOI] [PMID: 16232468]
3.	Nidetzky, B., Mayr, P., Hadwiger, P. and Stutz, A.E. Binding energy and specificity in the catalytic mechanism of yeast aldose reductases. Biochem. J. 344 Pt 1 (1999) 101–107. [PMID: 10548539]
4.	Mayr, P., Bruggler, K., Kulbe, K.D. and Nidetzky, B. D-Xylose metabolism by Candida intermedia: isolation and characterisation of two forms of aldose reductase with different coenzyme specificities. J. Chromatogr. B Biomed. Sci. Appl. 737 (2000) 195–202. [DOI] [PMID: 10681056]
5.	Sene, L., Felipe, M.G., Silva, S.S. and Vitolo, M. Preliminary kinetic characterization of xylose reductase and xylitol dehydrogenase extracted from Candida guilliermondii FTI 20037 cultivated in sugarcane bagasse hydrolysate for xylitol production. Appl. Biochem. Biotechnol. 91-93 (2001) 671–680. [DOI] [PMID: 11963895]
6.	Jeong, E.Y., Sopher, C., Kim, I.S. and Lee, H. Mutational study of the role of tyrosine-49 in the Saccharomyces cerevisiae xylose reductase. Yeast 18 (2001) 1081–1089. [DOI] [PMID: 11481678]
7.	Chroumpi, T., Peng, M., Aguilar-Pontes, M.V., Muller, A., Wang, M., Yan, J., Lipzen, A., Ng, V., Grigoriev, I.V., Makela, M.R. and de Vries, R.P. Revisiting a ‘simple’ fungal metabolic pathway reveals redundancy, complexity and diversity. Microb. Biotechnol. 14 (2021) 2525–2537. [DOI] [PMID: 33666344]
8.	Terebieniec, A., Chroumpi, T., Dilokpimol, A., Aguilar-Pontes, M.V., Makela, M.R. and de Vries, R.P. Characterization of D-xylose reductase, XyrB, from Aspergillus niger. Biotechnol Rep (Amst) 30:e00610 (2021). [DOI] [PMID: 33842213]

[EC 1.1.1.431 created 2022]

1.1.1.432

Accepted name:

6-dehydroglucose reductase

Reaction:

D-glucose + NADP⁺ = 6-dehydro-D-glucose + NADPH + H⁺

Glossary:

quinovose = 6-deoxy-D-glucopyranose

Other name(s):

D-glucose 6-dehydrogenase; smoB (gene name); squF (gene name)

Systematic name:

D-glucose:NADP⁺ 6-oxidoreductase

Comments:

The enzyme, characterized from alphaproteobacteria, is involved in a D-sulfoquinovose degradation pathway.

Links to other databases:

References:

Sharma, M., Lingford, J.P., Petricevic, M., Snow, A.J.D., Zhang, Y., Jarva, M.A., Mui, J.W., Scott, N.E., Saunders, E.C., Mao, R., Epa, R., da Silva, B.M., Pires, D.E.V., Ascher, D.B., McConville, M.J., Davies, G.J., Williams, S.J. and Goddard-Borger, E.D. Oxidative desulfurization pathway for complete catabolism of sulfoquinovose by bacteria. Proc. Natl. Acad. Sci. USA 119 (2022) e2116022119. [DOI] [PMID: 35074914]

Liu, J., Wei, Y., Ma, K., An, J., Liu, X., Liu, Y., Ang, E.L., Zhao, H. and Zhang, Y. Mechanistically diverse pathways for sulfoquinovose degradation in bacteria. ACS Catal. 11 (2021) 14740–14750. [DOI]

[EC 1.1.1.432 created 2022]

1.1.1.433

Accepted name:

sulfoacetaldehyde reductase (NADH)

Reaction:

isethionate + NAD⁺ = 2-sulfoacetaldehyde + NADH + H⁺

Glossary:

isethionate = 2-hydroxyethanesulfonate
2-sulfoacetaldehyde = 2-oxoethanesulfonate

Other name(s):

sarD (gene name); tauF (gene name); sqwF (gene name); BkTauF

Systematic name:

isethionate:NAD⁺ oxidoreductase

Comments:

The enzymes from the bacteria Bilophila wadsworthia and Clostridium sp. MSTE9 catalyse the reaction only in the reduction direction. In the bacterium Bifidobacterium kashiwanohense the optimal reaction pH for sulfoacetaldehyde reduction is 7.5, while that for isethionate oxidation is 10.0. cf. EC 1.1.1.313, sulfoacetaldehyde reductase (NADPH).

Links to other databases:

References:

1.	Peck, S.C., Denger, K., Burrichter, A., Irwin, S.M., Balskus, E.P. and Schleheck, D. A glycyl radical enzyme enables hydrogen sulfide production by the human intestinal bacterium Bilophila wadsworthia. Proc. Natl. Acad. Sci. USA 116 (2019) 3171–3176. [DOI] [PMID: 30718429]
2.	Xing, M., Wei, Y., Zhou, Y., Zhang, J., Lin, L., Hu, Y., Hua, G.,, N. Nanjaraj Urs, A., Liu, D., Wang, F., Guo, C., Tong, Y., Li, M., Liu, Y., Ang, E.L., Zhao, H., Yuchi, Z. and Zhang, Y. Radical-mediated C-S bond cleavage in C₂ sulfonate degradation by anaerobic bacteria. Nat. Commun. 10:1609 (2019). [DOI] [PMID: 30962433]
3.	Zhou, Y., Wei, Y., Nanjaraj Urs, A.N., Lin, L., Xu, T., Hu, Y., Ang, E.L., Zhao, H., Yuchi, Z. and Zhang, Y. Identification and characterization of a new sulfoacetaldehyde reductase from the human gut bacterium Bifidobacterium kashiwanohense. Biosci. Rep. 39 (2019) . [DOI] [PMID: 31123167]
4.	Liu, J., Wei, Y., Ma, K., An, J., Liu, X., Liu, Y., Ang, E.L., Zhao, H. and Zhang, Y. Mechanistically diverse pathways for sulfoquinovose degradation in bacteria. ACS Catal. 11 (2021) 14740–14750. [DOI]

[EC 1.1.1.433 created 2022]

1.1.2.11

Accepted name:

glucoside 3-dehydrogenase (cytochrome c)

Reaction:

a D-glucoside + a ferric c-type cytochrome = a 3-dehydro-D-glucoside + a ferrous c-type cytochrome

Other name(s):

D-glucoside 3-dehydrogenase (ambiguous); D-aldohexopyranoside dehydrogenase (ambiguous); D-aldohexoside:cytochrome c oxidoreductase; hexopyranoside-cytochrome c oxidoreductase

Systematic name:

a D-glucoside:ferric c-type cytochrome 3-oxidoreductase

Comments:

This bacterial enzyme acts on D-glucose, D-galactose, D-glucosides and D-galactosides, but the best substrates are disaccharides with a glucose moiety at the non-reducing end. It consists of two subunits, a catalytic subunit that contains an FAD cofactor and an iron-sulfur cluster, and a "hitch-hiker" subunit containing a signal peptide for translocation into the periplasm. A dedicated c-type cytochrome protein serves as an electron acceptor, transferring the electrons from the catalytic subunit to the cell's electron transfer chain. cf. EC 1.1.99.13, glucoside 3-dehydrogenase (acceptor).

Links to other databases:

BRENDA, EXPASY, GTD, KEGG

References:

1.	Hayano, K. and Fukui, S. Purification and properties of 3-ketosucrose-forming enzyme from the cells of Agrobacterium tumefaciens. J. Biol. Chem. 242 (1967) 3665–3672. [PMID: 6038493]
2.	Nakamura, L.K. and Tyler, D.D. Induction of D-aldohexoside:cytochrome c oxidoreductase in Agrobacterium tumefaciens. J. Bacteriol. 129 (1977) 830–835. [DOI] [PMID: 838689]
3.	Takeuchi, M., Ninomiya, K., Kawabata, K., Asano, N., Kameda, Y. and Matsui, K. Purification and properties of glucoside 3-dehydrogenase from Flavobacterium saccharophilum. J. Biochem. 100 (1986) 1049–1055. [DOI] [PMID: 3818559]
4.	Takeuchi, M., Asano, N., Kameda, Y. and Matsui, K. Physiological role of glucoside 3-dehydrogenase and cytochrome c₅₅₁ in the sugar oxidizing system of Flavobacterium saccharophilum. J. Biochem. 103 (1988) 938–943. [DOI] [PMID: 2844746]
5.	Tsugawa, W., Horiuchi, S., Tanaka, M., Wake, H. and Sode, K. Purification of a marine bacterial glucose dehydrogenase from Cytophaga marinoflava and its application for measurement of 1,5-anhydro-D-glucitol. Appl. Biochem. Biotechnol. 56 (1996) 301–310. [DOI] [PMID: 8984902]
6.	Kojima, K., Tsugawa, W. and Sode, K. Cloning and expression of glucose 3-dehydrogenase from Halomonas sp. α-15 in Escherichia coli. Biochem. Biophys. Res. Commun. 282 (2001) 21–27. [DOI] [PMID: 11263965]
7.	Zhang, J.F., Zheng, Y.G., Xue, Y.P. and Shen, Y.C. Purification and characterization of the glucoside 3-dehydrogenase produced by a newly isolated Stenotrophomonas maltrophilia CCTCC M 204024. Appl. Microbiol. Biotechnol. 71 (2006) 638–645. [DOI] [PMID: 16292530]
8.	Zhang, J.F., Chen, W.Q. and Chen, H. Gene cloning and expression of a glucoside 3-dehydrogenase from Sphingobacterium faecium ZJF-D6, and used it to produce N-p-nitrophenyl-3-ketovalidamine. World J. Microbiol. Biotechnol. 33:21 (2017). [DOI] [PMID: 28044272]
9.	Miyazaki, R., Yamazaki, T., Yoshimatsu, K., Kojima, K., Asano, R., Sode, K. and Tsugawa, W. Elucidation of the intra- and inter-molecular electron transfer pathways of glucoside 3-dehydrogenase. Bioelectrochemistry 122 (2018) 115–122. [DOI] [PMID: 29625423]

[EC 1.1.2.11 created 2022]

1.1.3.50

Accepted name:

C-glycoside oxidase

Reaction:

carminate + O₂ = 3′-dehydrocarminate + H₂O₂

For diagram of carminate catabolism, click here

Glossary:

carminate = 7-(β-D-glucopyranosyl)-3,5,6,8-tetrahydroxy-1-methyl-9,10-dioxo-9,10-dihydroanthracene-2-carboxylate

Other name(s):

carA (gene name)

Systematic name:

carminate:oxygen 3′-oxidoreductase (H₂O₂-forming)

Comments:

A flavoprotein (FAD). This bacterial enzyme participates in degradation of certain C-glucosides by catalysing the oxidation of the hydroxyl group at position 3 of the glycose moiety. The enzyme was found active with assorted C-glycosides, such as carminate, mangiferin, and C⁶-glycosylated flavonoids, but not with D-glucose or C⁸-glycosylated flavonoids.

Links to other databases:

References:

Kumano, T., Hori, S., Watanabe, S., Terashita, Y., Yu, H.Y., Hashimoto, Y., Senda, T., Senda, M. and Kobayashi, M. FAD-dependent C-glycoside-metabolizing enzymes in microorganisms: Screening, characterization, and crystal structure analysis. Proc. Natl. Acad. Sci. USA 118(40) (2021) e2106580118. [DOI] [PMID: 34583991]

[EC 1.1.3.50 created 2022]

*EC

1.1.99.13

Accepted name:

glucoside 3-dehydrogenase (acceptor)

Reaction:

sucrose + acceptor = 3-dehydro-α-D-glucosyl-β-D-fructofuranoside + reduced acceptor

Other name(s):

D-glucoside 3-dehydrogenase (ambiguous); D-aldohexopyranoside dehydrogenase (ambiguous); D-aldohexoside:(acceptor) 3-oxidoreductase; thuA (gene name); thuB (gene name); glucoside 3-dehydrogenase

Systematic name:

D-aldohexoside:acceptor 3-oxidoreductase

Comments:

The enzymes from members of the Rhizobiaceae family (such as Agrobacterium tumefaciens) act on disaccharides that contain a glucose moiety at the non-reducing end, such as sucrose, trehalose, leucrose, palatinose, trehalulose, and maltitol, forming the respective 3′-keto derivatives. cf. EC 1.1.2.11, glucoside 3-dehydrogenase (cytochrome c).

Links to other databases:

BRENDA, EXPASY, Gene, GTD, KEGG, CAS registry number: 9031-74-7

References:

1.	Jensen, J.B., Ampomah, O.Y., Darrah, R., Peters, N.K. and Bhuvaneswari, T.V. Role of trehalose transport and utilization in Sinorhizobium meliloti-alfalfa interactions. Mol. Plant Microbe Interact. 18 (2005) 694–702. [DOI] [PMID: 16042015]
2.	Ampomah, O.Y., Avetisyan, A., Hansen, E., Svenson, J., Huser, T., Jensen, J.B. and Bhuvaneswari, T.V. The thuEFGKAB operon of Rhizobia and Agrobacterium tumefaciens codes for transport of trehalose, maltitol, and isomers of sucrose and their assimilation through the formation of their 3-keto derivatives. J. Bacteriol. 195 (2013) 3797–3807. [DOI] [PMID: 23772075]
3.	Ampomah, O.Y. and Jensen, J.B. The trehalose utilization gene thuA ortholog in Mesorhizobium loti does not influence competitiveness for nodulation on Lotus spp. World J. Microbiol. Biotechnol. 30 (2014) 1129–1134. [DOI] [PMID: 24142427]

[EC 1.1.99.13 created 1972, modified 2022]

*EC

1.3.5.1

Accepted name:

succinate dehydrogenase

Reaction:

succinate + a quinone = fumarate + a quinol

For diagram of the citric acid cycle, click here

Other name(s):

succinate dehydrogenase (quinone); succinate dehydrogenase (ubiquinone); succinic dehydrogenase; complex II (ambiguous); succinate dehydrogenase complex; SDH (ambiguous); succinate:ubiquinone oxidoreductase; fumarate reductase (quinol); FRD; menaquinol-fumarate oxidoreductase; succinate dehydrogenase (menaquinone); succinate:menaquinone oxidoreductase; fumarate reductase (menaquinone)

Systematic name:

succinate:quinone oxidoreductase

Comments:

A complex generally comprising an FAD-containing component that also binds the carboxylate substrate (A subunit), a component that contains three different iron-sulfur centers [2Fe-2S], [4Fe-4S], and [3Fe-4S] (B subunit), and a hydrophobic membrane-anchor component (C, or C and D subunits) that is also the site of the interaction with quinones. The enzyme is found in the inner mitochondrial membrane in eukaryotes and the plasma membrane of bacteria and archaea, with the hydrophilic domain extending into the mitochondrial matrix and the cytoplasm, respectively. Under aerobic conditions the enzyme catalyses succinate oxidation, a key step in the citric acid (TCA) cycle, transferring the electrons to quinones in the membrane, thus linking the TCA cycle with the aerobic respiratory chain (where it is known as complex II). Under anaerobic conditions the enzyme functions as a fumarate reductase, transferring electrons from the quinol pool to fumarate, and participating in anaerobic respiration with fumarate as the terminal electron acceptor. The enzyme interacts with the quinone produced by the organism, such as ubiquinone, menaquinone, caldariellaquinone, thermoplasmaquinone, rhodoquinone etc. Some of the enzymes contain two heme subunits in their membrane anchor subunit. These enzymes catalyse an electrogenic reaction and are thus classified as EC 7.1.1.12, succinate dehydrogenase (electrogenic, proton-motive force generating).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9028-11-9

References:

1.	Kita, K., Vibat, C.R., Meinhardt, S., Guest, J.R. and Gennis, R.B. One-step purification from Escherichia coli of complex II (succinate: ubiquinone oxidoreductase) associated with succinate-reducible cytochrome b₅₅₆. J. Biol. Chem. 264 (1989) 2672–2677. [PMID: 2644269]
2.	Van Hellemond, J.J. and Tielens, A.G. Expression and functional properties of fumarate reductase. Biochem. J. 304 (1994) 321–331. [PMID: 7998964]
3.	Iverson, T.M., Luna-Chavez, C., Cecchini, G. and Rees, D.C. Structure of the Escherichia coli fumarate reductase respiratory complex. Science 284 (1999) 1961–1966. [DOI] [PMID: 10373108]
4.	Cecchini, G., Schroder, I., Gunsalus, R.P. and Maklashina, E. Succinate dehydrogenase and fumarate reductase from Escherichia coli. Biochim. Biophys. Acta 1553 (2002) 140–157. [DOI] [PMID: 11803023]
5.	Figueroa, P., Leon, G., Elorza, A., Holuigue, L., Araya, A. and Jordana, X. The four subunits of mitochondrial respiratory complex II are encoded by multiple nuclear genes and targeted to mitochondria in Arabidopsis thaliana. Plant Mol. Biol. 50 (2002) 725–734. [PMID: 12374303]
6.	Cecchini, G. Function and structure of complex II of the respiratory chain. Annu. Rev. Biochem. 72 (2003) 77–109. [DOI] [PMID: 14527321]
7.	Oyedotun, K.S. and Lemire, B.D. The quaternary structure of the Saccharomyces cerevisiae succinate dehydrogenase. Homology modeling, cofactor docking, and molecular dynamics simulation studies. J. Biol. Chem. 279 (2004) 9424–9431. [DOI] [PMID: 14672929]
8.	Kurokawa, T. and Sakamoto, J. Purification and characterization of succinate:menaquinone oxidoreductase from Corynebacterium glutamicum. Arch. Microbiol. 183 (2005) 317–324. [DOI] [PMID: 15883782]
9.	Iwata, F., Shinjyo, N., Amino, H., Sakamoto, K., Islam, M.K., Tsuji, N. and Kita, K. Change of subunit composition of mitochondrial complex II (succinate-ubiquinone reductase/quinol-fumarate reductase) in Ascaris suum during the migration in the experimental host. Parasitol Int 57 (2008) 54–61. [DOI] [PMID: 17933581]

[EC 1.3.5.1 created 1983 (EC 1.3.99.1 created 1961, incorporated 2014, EC 1.3.5.4 created 2010, incorporated 2022), modified 2022]

1.3.5.4

Transferred entry:

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

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

*EC

1.4.1.21

Accepted name:

aspartate dehydrogenase

Reaction:

L-aspartate + H₂O + NAD(P)⁺ = oxaloacetate + NH₃ + NAD(P)H + H⁺ (overall reaction)
(1a) L-aspartate + NAD(P)⁺ = 2-iminosuccinate + NAD(P)H + H⁺
(1b) 2-iminosuccinate + H₂O = oxaloacetate + NH₃ (spontaneous)

Other name(s):

AspDH; NAD-dependent aspartate dehydrogenase; NADH₂-dependent aspartate dehydrogenase; NADP⁺-dependent aspartate dehydrogenase; nadX (gene name); L-aspartate:NAD(P)⁺ oxidoreductase (deaminating)

Systematic name:

L-aspartate:NAD(P)⁺ oxidoreductase (2-iminosuccinate-forming)

Comments:

The enzyme is strictly specific for L-aspartate as substrate. It produces the unstable compound 2-iminosuccinate, which, in the presence of water, hydrolyses spontaneously to form oxaloacetate. The enzyme from some archaea and thermophilic bacteria is likely to transfer 2-iminosuccinate directly to EC 2.5.1.72, quinolinate synthase, preventing its hydrolysis and enabling the de novo biosynthesis of NAD⁺.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 37278-97-0

References:

1.	Kretovich, W.L., Kariakina, T.I., Weinova, M.K., Sidelnikova, L.I. and Kazakova, O.W. The synthesis of aspartic acid in Rhizobium lupini bacteroids. Plant Soil 61 (1981) 145–156.
2.	Okamura, T., Noda, H., Fukuda, S. and Ohsugi, M. Aspartate dehydrogenase in vitamin B₁₂-producing Klebsiella pneumoniae IFO 13541. J. Nutr. Sci. Vitaminol. 44 (1998) 483–490. [PMID: 9819709]
3.	Yang, Z., Savchenko, A., Yakunin, A., Zhang, R., Edwards, A., Arrowsmith, C. and Tong, L. Aspartate dehydrogenase, a novel enzyme identified from structural and functional studies of TM1643. J. Biol. Chem. 278 (2003) 8804–8808. [DOI] [PMID: 12496312]
4.	Yoneda, K., Kawakami, R., Tagashira, Y., Sakuraba, H., Goda, S. and Ohshima, T. The first archaeal L-aspartate dehydrogenase from the hyperthermophile Archaeoglobus fulgidus: gene cloning and enzymological characterization. Biochim. Biophys. Acta 1764 (2006) 1087–1093. [DOI] [PMID: 16731057]
5.	Yoneda, K., Sakuraba, H., Tsuge, H., Katunuma, N. and Ohshima, T. Crystal structure of archaeal highly thermostable L-aspartate dehydrogenase/NAD/citrate ternary complex. FEBS J. 274 (2007) 4315–4325. [DOI] [PMID: 17651440]
6.	Li, Y., Kawakami, N., Ogola, H.J., Ashida, H., Ishikawa, T., Shibata, H. and Sawa, Y. A novel L-aspartate dehydrogenase from the mesophilic bacterium Pseudomonas aeruginosa PAO1: molecular characterization and application for L-aspartate production. Appl. Microbiol. Biotechnol. 90 (2011) 1953–1962. [DOI] [PMID: 21468714]
7.	Li, Y., Ishida, M., Ashida, H., Ishikawa, T., Shibata, H. and Sawa, Y. A non-NadB type L-aspartate dehydrogenase from Ralstonia eutropha strain JMP134: molecular characterization and physiological functions. Biosci. Biotechnol. Biochem. 75 (2011) 1524–1532. [DOI] [PMID: 21821928]
8.	Li, Y., Ogola, H.J. and Sawa, Y. L-aspartate dehydrogenase: features and applications. Appl. Microbiol. Biotechnol. 93 (2012) 503–516. [DOI] [PMID: 22120624]

[EC 1.4.1.21 created 2005, modified 2022]

1.4.1.28

Accepted name:

secondary-alkyl amine dehydrogenase [NAD(P)⁺]

Reaction:

a secondary-alkyl amine + H₂O + NAD(P)⁺ = a ketone + NH₃ + NAD(P)H + H⁺

Glossary:

a secondary-alkyl amine = RCHNH₂R′

Other name(s):

AmDH (ambiguous); amine dehydrogenase (ambiguous)

Systematic name:

secondary-alkyl amine:NAD(P)⁺ oxidoreductase (deaminating)

Comments:

The enzyme has been shown to react preferentially with short-chain ketones such as cyclohexanone, primary amine groups attached to secondary alkyl groups, or D- and L-amino acids. It also reduces aldehydes to primary amines. Cosubstrate preference depends on the substrate.

Links to other databases:

References:

1.	Itoh, N., Yachi, C. and Kudome, T. Determining a novel NAD⁺-dependent amine dehydrogenase with a broad substrate range from Streptomyces virginiae IFO 12827: purification and characterization. Journal of Molecular Catalysis B: Enzymatic 10 (2000) 281–290. [DOI]
2.	Mayol, O., David, S., Darii, E., Debard, A., Mariage, A., Pellouin, V., Petit, J.L., Salanoubat, M., de Berardinis, V., Zaparucha, A. and Vergne-Vaxelaire, C. Asymmetric reductive amination by a wild-type amine dehydrogenase from the thermophilic bacteria Petrotoga mobilis. Catalysis Science & Technology 6 (2016) 7421–7428. [DOI]
3.	Mayol, O., Bastard, K., Beloti, L., Frese, A., Turkenburg, J.P., Petit, J.L., Mariage, A., Debard, A., Pellouin, V., Perret, A., de Berardinis, V., Zaparucha, A., Grogan, G. and Vergne-Vaxelaire, C. A family of native amine dehydrogenases for the asymmetric reductive amination of ketones. Nature Catalysis 2 (2019) 324–333. [DOI]
4.	Lee, S., Jeon, H., Giri, P., Lee, U.J., Jung, H., Lim, S., Sarak, S., Khobragade, T.P., Kim, B.G. and Yun, H. The reductive amination of carbonyl compounds using native amine dehydrogenase from Laribacter hongkongensis. Biotechnol. Bioprocess Eng. 26 (2021) 384–391. [DOI]

[EC 1.4.1.28 created 2022]

*EC

1.5.3.10

Accepted name:

dimethylglycine oxidase

Reaction:

N,N-dimethylglycine + 5,6,7,8-tetrahydrofolate + O₂ = sarcosine + 5,10-methylenetetrahydrofolate + H₂O₂

Other name(s):

dmg (gene name); N,N-dimethylglycine:oxygen oxidoreductase (demethylating)

Systematic name:

N,N-dimethylglycine,5,6,7,8-tetrahydrofolate:oxygen oxidoreductase (demethylating,5,10-methylenetetrahydrofolate-forming)

Comments:

A flavoprotein (FAD). The enzyme, characterized from the bacterium Arthrobacter globiformis, contains two active sites connected by a large "reaction chamber". An imine intermediate is transferred between the sites, eliminating the production of toxic formaldehyde. In the absence of folate the enzyme does form formaldehyde. Does not oxidize sarcosine. cf. EC 1.5.8.4, dimethylglycine dehydrogenase.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 37256-30-7

References:

1.	Mori, N., Kawakami, B., Tani, Y. and Yamada, H. Purification and properties of dimethylglycine oxidase from Cylindrocarpon didymum M-1. Agric. Biol. Chem. 44 (1980) 1383–1389.
2.	Meskys, R., Harris, R.J., Casaite, V., Basran, J. and Scrutton, N.S. Organization of the genes involved in dimethylglycine and sarcosine degradation in Arthrobacter spp.: implications for glycine betaine catabolism. Eur. J. Biochem. 268 (2001) 3390–3398. [DOI] [PMID: 11422368]
3.	Basran, J., Bhanji, N., Basran, A., Nietlispach, D., Mistry, S., Meskys, R. and Scrutton, N.S. Mechanistic aspects of the covalent flavoprotein dimethylglycine oxidase of Arthrobacter globiformis studied by stopped-flow spectrophotometry. Biochemistry 41 (2002) 4733–4743. [DOI] [PMID: 11926836]
4.	Leys, D., Basran, J. and Scrutton, N.S. Channelling and formation of ‘active’ formaldehyde in dimethylglycine oxidase. EMBO J. 22 (2003) 4038–4048. [DOI] [PMID: 12912903]
5.	Basran, J., Fullerton, S., Leys, D. and Scrutton, N.S. Mechanism of FAD reduction and role of active site residues His-225 and Tyr-259 in Arthrobacter globiformis dimethylglycine oxidase: analysis of mutant structure and catalytic function. Biochemistry 45 (2006) 11151–11161. [DOI] [PMID: 16964976]
6.	Tralau, T., Lafite, P., Levy, C., Combe, J.P., Scrutton, N.S. and Leys, D. An internal reaction chamber in dimethylglycine oxidase provides efficient protection from exposure to toxic formaldehyde. J. Biol. Chem. 284 (2009) 17826–17834. [DOI] [PMID: 19369258]
7.	Casaite, V., Poviloniene, S., Meskiene, R., Rutkiene, R. and Meskys, R. Studies of dimethylglycine oxidase isoenzymes in Arthrobacter globiformis cells. Curr. Microbiol. 62 (2011) 1267–1273. [DOI] [PMID: 21188587]

[EC 1.5.3.10 created 1992, modified 2022]

1.5.3.25

Accepted name:

fructosyl amine oxidase (glucosone-forming)

Reaction:

an N-(1-deoxy-D-fructos-1-yl)amine + O₂ + H₂O = D-glucosone + an amine + H₂O₂ (overall reaction)
(1a) an N-(1-deoxy-D-fructos-1-yl)amine + O₂ = a 2-[(3S,4R,5R)-3,4,5,6-tetrahydroxy-2-oxohexylidene]amine + H₂O₂
(1b) a 2-[(3S,4R,5R)-3,4,5,6-tetrahydroxy-2-oxohexylidene]amine + H₂O = D-glucosone + an amine (spontaneous)

Other name(s):

amadoriase

Systematic name:

N-(1-deoxy-D-fructos-1-yl)amine:oxygen 2-oxidoreductase (glucosone-forming)

Comments:

Reducing sugars such as glucose react with amino groups in proteins via the spontaeous Maillard reaction, forming an unstable product that undergoes spontaneous rearrangement to a keto amine compound. These reactions are known as glycation reactions, and the stable products are known as Amadori products. This enzyme, which contains an FAD cofactor, catalyses a deglycation reaction that regenerates the amine reactant. By-products are glucosone and hydrogen peroxide. The enzymes have been reported from fungi and bacteria, but not from higher eukaryotes. Specific enzymes differ in their substrate specificity. cf. EC 1.5.3.26, fructosyl amine oxidase (fructosamine-forming).

Links to other databases:

References:

1.	Horiuchi, T., Kurokawa, T. and Saito, N. Purification and properties of fructosyl-amino acid oxidase from Corynebacterium sp. 2-4-1. Agr Biol Chem Tokyo 53 (1989) 103–110. [DOI]
2.	Takahashi, M., Pischetsrieder, M. and Monnier, V.M. Molecular cloning and expression of amadoriase isoenzyme (fructosyl amine:oxygen oxidoreductase, EC 1.5.3) from Aspergillus fumigatus. J. Biol. Chem. 272 (1997) 12505–12507. [DOI] [PMID: 9139700]
3.	Hirokawa, K. and Kajiyama, N. Recombinant agrobacterium AgaE-like protein with fructosyl amino acid oxidase activity. Biosci. Biotechnol. Biochem. 66 (2002) 2323–2329. [DOI] [PMID: 12506967]
4.	Wu, X. and Monnier, V.M. Enzymatic deglycation of proteins. Arch. Biochem. Biophys. 419 (2003) 16–24. [DOI] [PMID: 14568004]
5.	Sakaue, R., Nakatsu, T., Yamaguchi, Y., Kato, H. and Kajiyama, N. Crystallization and preliminary crystallographic analysis of bacterial fructosyl amino acid oxidase. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 61 (2005) 196–198. [DOI] [PMID: 16510992]

[EC 1.5.3.25 created 2022]

1.5.3.26

Accepted name:

fructosyl amine oxidase (fructosamine-forming)

Reaction:

an N-(1-deoxy-D-fructos-1-yl)amine + O₂ + H₂O = (1-deoxy-D-fructos-1-yl)amine + an aldehyde + H₂O₂

Systematic name:

N-(1-deoxy-D-fructos-1-yl)amine:oxygen oxidoreductase (fructosamine-forming)

Comments:

Reducing sugars such as glucose react with amino groups in proteins via the spontaeous Maillard reaction, forming an unstable product that undergoes spontaneous rearrangement to a keto amine compound. These reactions are known as glycation reactions, and the stable products are known as Amadori products. This enzyme, characterized from a Pseudomonas sp. strain, cleaves the Amadori products at the alkylamine bond. All other known fructosyl amine oxidases cleave the ketoamine bond (cf. EC 1.5.3.25, fructosyl amine oxidase (glucosone-forming)).

Links to other databases:

References:

1.	Gerhardinger, C., Marion, M.S., Rovner, A., Glomb, M. and Monnier, V.M. Novel degradation pathway of glycated amino acids into free fructosamine by a Pseudomonas sp. soil strain extract. J. Biol. Chem. 270 (1995) 218–224. [DOI] [PMID: 7814378]
2.	Saxena, A.K., Saxena, P. and Monnier, V.M. Purification and characterization of a membrane-bound deglycating enzyme (1-deoxyfructosyl alkyl amino acid oxidase, EC 1.5.3) from a Pseudomonas sp. soil strain. J. Biol. Chem. 271 (1996) 32803–32809. [DOI] [PMID: 8955117]
3.	Wu, X. and Monnier, V.M. Enzymatic deglycation of proteins. Arch. Biochem. Biophys. 419 (2003) 16–24. [DOI] [PMID: 14568004]

[EC 1.5.3.26 created 2022]

1.5.7.3

Accepted name:

N,N-dimethylglycine/sarcosine dehydrogenase (ferredoxin)

Reaction:

(1) N,N-dimethylglycine + 2 oxidized ferredoxin + H₂O = sarcosine + formaldehyde + 2 reduced ferredoxin + 2 H⁺
(2) sarcosine + 2 oxidized ferredoxin + H₂O = glycine + formaldehyde + 2 reduced ferredoxin + 2 H⁺

Other name(s):

ddhC (gene name); dgcA (gene name)

Systematic name:

N,N-dimethylglycine/sarcosine:ferredoxin oxidoreductase (demethylating)

Comments:

This bacterial enzyme is involved in degradation of glycine betaine. The enzyme contains non-covalently bound FAD and NAD(P) cofactors, and catalyses the demethylation of both N,N-dimethylglycine and sarcosine, releasing formaldehyde and forming glycine as the final product. The enzyme can utilize both NAD⁺ and NADP⁺, but the catalytic efficiency with NAD⁺ is ~5-fold higher. The native electron acceptor of the enzyme is a membrane-bound clostridial-type ferredoxin, which transfers the electrons to an electron-transfer flavoprotein (ETF).

Links to other databases:

References:

1.	Wargo, M.J., Szwergold, B.S. and Hogan, D.A. Identification of two gene clusters and a transcriptional regulator required for Pseudomonas aeruginosa glycine betaine catabolism. J. Bacteriol. 190 (2008) 2690–2699. [DOI] [PMID: 17951379]
2.	Yang, T., Shao, Y.H., Guo, L.Z., Meng, X.L., Yu, H. and Lu, W.D. Role of N,N-dimethylglycine and its catabolism to sarcosine in Chromohalobacter salexigens DSM 3043. Appl. Environ. Microbiol. 86 (2020) . [DOI] [PMID: 32631860]

[EC 1.5.7.3 created 2022]

1.8.1.3

Deleted entry:

hypotaurine dehydrogenase. The reaction is now known to be catalyzed by EC 1.14.13.8, flavin-containing monooxygenase.

[EC 1.8.1.3 created 1972, deleted 2022]

1.13.11.93

Accepted name:

2-oxoadipate dioxygenase/decarboxylase

Reaction:

2-oxoadipate + O₂ = (R)-2-hydroxyglutarate + CO₂

Other name(s):

ydcJ (gene name)

Systematic name:

2-oxoadipate dioxygenase/carboxy lyase

Comments:

The enzyme, characterized from the bacterium Pseudomonas putida, is involved in an L-lysine catabolic pathway. Contains Fe(II).

Links to other databases:

References:

Thompson, M.G., Blake-Hedges, J.M., Cruz-Morales, P., Barajas, J.F., Curran, S.C., Eiben, C.B., Harris, N.C., Benites, V.T., Gin, J.W., Sharpless, W.A., Twigg, F.F., Skyrud, W., Krishna, R.N., Pereira, J.H., Baidoo, E.EK., Petzold, C.J., Adams, P.D., Arkin, A.P., Deutschbauer, A.M. and Keasling, J.D. Massively parallel fitness profiling reveals multiple novel enzymes in Pseudomonas putida lysine metabolism. mBio 10 (2019) . [DOI] [PMID: 31064836]

[EC 1.13.11.93 created 2022]

1.14.11.78

Accepted name:

(R)-3-[(carboxymethyl)amino]fatty acid dioxygenase/decarboxylase

Reaction:

a (3R)-3-[(carboxylmethyl)amino]fatty acid + 2 2-oxoglutarate + 2 O₂ = a (3R)-3-isocyanyl-fatty acid + 2 succinate + 3 CO₂ + 2 H₂O (overall reaction)
(1a) a (3R)-3-[(carboxylmethyl)amino]fatty acid + 2-oxoglutarate + O₂ = a (3R)-3-{[carboxy(hydroxy)methyl]amino}fatty acid + succinate + CO₂
(1b) a (3R)-3-{[carboxy(hydroxy)methyl]amino}fatty acid + 2-oxoglutarate + O₂ = a (3R)-3-isocyanyl-fatty acid + succinate + 2 CO₂ + 2 H₂O

Other name(s):

scoE (gene name); mmaE (gene name); Rv0097 (locus name)

Systematic name:

(3R)-3-[(carboxylmethyl)amino]fatty acid,2-oxoglutarate:oxygen oxidoreductase (isonitrile-forming)

Comments:

Requires Fe(II). The enzyme, found in actinobacterial species, participates in the biosynthesis of isonitrile-containing lipopeptides. The reaction comprises two catalytic cycles, each consuming an oxygen molecule and a 2-oxoglutarate molecule. In the first cycle the substrate is hydroxylated, while in the second cycle the enzyme catalyses a decarboxylation/oxidation reaction that produces an isonitrile group.

Links to other databases:

References:

1.	Harris, N.C., Sato, M., Herman, N.A., Twigg, F., Cai, W., Liu, J., Zhu, X., Downey, J., Khalaf, R., Martin, J., Koshino, H. and Zhang, W. Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria. Proc. Natl. Acad. Sci. USA 114 (2017) 7025–7030. [DOI] [PMID: 28634299]
2.	Harris, N.C., Born, D.A., Cai, W., Huang, Y., Martin, J., Khalaf, R., Drennan, C.L. and Zhang, W. Isonitrile formation by a non-heme iron(II)-dependent oxidase/decarboxylase. Angew. Chem. Int. Ed. Engl. 57 (2018) 9707–9710. [DOI] [PMID: 29906336]
3.	Jonnalagadda, R., Del Rio Flores, A., Cai, W., Mehmood, R., Narayanamoorthy, M., Ren, C., Zaragoza, J.PT., Kulik, H.J., Zhang, W. and Drennan, C.L. Biochemical and crystallographic investigations into isonitrile formation by a nonheme iron-dependent oxidase/decarboxylase. J. Biol. Chem. 296:100231 (2021). [DOI] [PMID: 33361191]

[EC 1.14.11.78 created 2022]

1.14.11.79

Accepted name:

protein-L-histidine (3S)-3-hydroxylase

Reaction:

a [protein]-L-histidine + 2-oxoglutarate + O₂ = a [protein]-(3S)-3-hydroxy-L-histidine + succinate + CO₂

Other name(s):

RIOX1 (gene name); RIOX2 (gene name); protein histidyl hydroxylase

Systematic name:

protein-L-histidine,2-oxoglutarate:oxygen oxidoreductase (3S-hydroxylating)

Comments:

The human enzymes encoded by the RIOX1 and RIOX2 genes catalyse the hydroxylation of L-histidine residues in the 60S ribosomal proteins Rpl8 and L27a, respectively. Both proteins contain JmjC and winged helix domains, and both also catalyse histone L-lysine demethylation activities.

Links to other databases:

References:

Ge, W., Wolf, A., Feng, T., Ho, C.H., Sekirnik, R., Zayer, A., Granatino, N., Cockman, M.E., Loenarz, C., Loik, N.D., Hardy, A.P., Claridge, T.DW., Hamed, R.B., Chowdhury, R., Gong, L., Robinson, C.V., Trudgian, D.C., Jiang, M., Mackeen, M.M., Mccullagh, J.S., Gordiyenko, Y., Thalhammer, A., Yamamoto, A., Yang, M., Liu-Yi, P., Zhang, Z., Schmidt-Zachmann, M., Kessler, B.M., Ratcliffe, P.J., Preston, G.M., Coleman, M.L. and Schofield, C.J. Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humans. Nat. Chem. Biol. 8 (2012) 960–962. [DOI] [PMID: 23103944]

Bundred, J.R., Hendrix, E. and Coleman, M.L. The emerging roles of ribosomal histidyl hydroxylases in cell biology, physiology and disease. Cell. Mol. Life Sci. 75 (2018) 4093–4105. [DOI] [PMID: 30151692]

[EC 1.14.11.79 created 2022]

1.14.13.147

Transferred entry:

taxoid 7β-hydroxylase. Now EC 1.14.14.182, taxoid 7β-hydroxylase

[EC 1.14.13.147 created 2012, deleted 2022]

1.14.13.251

Accepted name:

glycine betaine monooxygenase

Reaction:

glycine betaine + NADH + H⁺ + O₂ = N,N-dimethylglycine + formaldehyde + NAD⁺ + H₂O

Other name(s):

glycine betaine dioxygenase (incorrect); bmoAB (gene names); gbcAB (gene names)

Systematic name:

glycine betaine,NADH:oxygen oxidoreductase (demethylating)

Comments:

The enzyme, characterized from the bacteria Pseudomonas aeruginosa and Chromohalobacter salexigens, is involved in a degradation pathway of glycine betaine. It is composed of two subunits - a ferredoxin reductase component that contains FAD, and a terminal oxygenase component that contains a [2Fe-2S] Rieske-type iron-sulfur cluster and a nonheme iron centre.

Links to other databases:

References:

1.	Wargo, M.J., Szwergold, B.S. and Hogan, D.A. Identification of two gene clusters and a transcriptional regulator required for Pseudomonas aeruginosa glycine betaine catabolism. J. Bacteriol. 190 (2008) 2690–2699. [DOI] [PMID: 17951379]
2.	Li, S., Yu, X. and Beattie, G.A. Glycine betaine catabolism contributes to Pseudomonas syringae tolerance to hyperosmotic stress by relieving betaine-mediated suppression of compatible solute synthesis. J. Bacteriol. 195 (2013) 2415–2423. [DOI] [PMID: 23524610]
3.	Shao, Y.H., Guo, L.Z., Zhang, Y.Q., Yu, H., Zhao, B.S., Pang, H.Q. and Lu, W.D. Glycine betaine monooxygenase, an unusual Rieske-type oxygenase system, catalyzes the oxidative N-demethylation of glycine betaine in Chromohalobacter salexigens DSM 3043. Appl. Environ. Microbiol. 84 (2018) . [DOI] [PMID: 29703733]

[EC 1.14.13.251 created 2022]

1.14.14.179

Accepted name:

brassinosteroid 6-oxygenase

Reaction:

6-deoxocastasterone + 2 O₂ + 2 [reduced NADPH—hemoprotein reductase] = castasterone + 3 H₂O + 2 [oxidized NADPH—hemoprotein reductase] (overall reaction)
(1a) 6-deoxocastasterone + O₂ + [reduced NADPH—hemoprotein reductase] = 6α-hydroxy-6-deoxocastasterone + H₂O + [oxidized NADPH—hemoprotein reductase]
(1b) 6α-hydroxy-6-deoxocastasterone + O₂ + [reduced NADPH—hemoprotein reductase] = castasterone + 2 H₂O + [oxidized NADPH—hemoprotein reductase]

For diagram of brassinolide biosynthesis, click here

Other name(s):

CYP85A1 (gene name); CYP85A2 (gene name); brassinosteroid 6-oxidase

Systematic name:

6-deoxocastasterone,NADPH—hemoprotein reductase:oxygen 6-oxidoreductase (castasterone-forming)

Comments:

This cytochrome P-450 (heme thiolate) plant enzyme catalyses the C-6 hydoxylation of several brassinosteroid biosynthesis intermediates, and the further oxidation of the hydroxyl group to an oxo group. Substrates include 6-deoxocastasterone, 6-deoxotyphasterol, 3-dehydro-6-deoxoteasterone, and 6-deoxoteasterone. The CYP85A2 isozyme of Arabidopsis thaliana (but not the CYP85A1 isozyme) also catalyses the activity of EC 1.14.14.180, brassinolide synthase.

Links to other databases:

References:

1.	Shimada, Y., Fujioka, S., Miyauchi, N., Kushiro, M., Takatsuto, S., Nomura, T., Yokota, T., Kamiya, Y., Bishop, G.J. and Yoshida, S. Brassinosteroid-6-oxidases from Arabidopsis and tomato catalyze multiple C-6 oxidations in brassinosteroid biosynthesis. Plant Physiol. 126 (2001) 770–779. [DOI] [PMID: 11402205]
2.	Perez-Espana, V.H., Sanchez-Leon, N. and Vielle-Calzada, J.P. CYP85A1 is required for the initiation of female gametogenesis in Arabidopsis thaliana. Plant Signal Behav. 6 (2011) 321–326. [DOI] [PMID: 21364326]

[EC 1.14.14.179 created 2022]

1.14.14.180

Accepted name:

brassinolide synthase

Reaction:

castasterone + O₂ + [reduced NADPH—hemoprotein reductase] = brassinolide + 2 H₂O + [oxidized NADPH—hemoprotein reductase]

For diagram of brassinolide biosynthesis, click here

Other name(s):

CYP85A2 (gene name); CYP85A3 (gene name)

Systematic name:

castasterone,NADPH—hemoprotein reductase:oxygen oxidoreductase (lactonizing, brassinolide-forming)

Comments:

This cytochrome P-450 (heme thiolate) plant enzyme catalyses the lactonization of several brassinosteroids, including castasterone, teasterone, and typhasterol. The CYP85A2 enzyme of Arabidopsis thaliana also catalyses the activity of EC 1.14.14.179, brassinosteroid 6-oxygenase.

Links to other databases:

References:

1.	Nomura, T., Kushiro, T., Yokota, T., Kamiya, Y., Bishop, G.J. and Yamaguchi, S. The last reaction producing brassinolide is catalyzed by cytochrome P-450s, CYP85A3 in tomato and CYP85A2 in Arabidopsis. J. Biol. Chem. 280 (2005) 17873–17879. [DOI] [PMID: 15710611]
2.	Kim, T.W., Hwang, J.Y., Kim, Y.S., Joo, S.H., Chang, S.C., Lee, J.S., Takatsuto, S. and Kim, S.K. Arabidopsis CYP85A2, a cytochrome P450, mediates the Baeyer-Villiger oxidation of castasterone to brassinolide in brassinosteroid biosynthesis. Plant Cell 17 (2005) 2397–2412. [DOI] [PMID: 16024588]
3.	Katsumata, T., Hasegawa, A., Fujiwara, T., Komatsu, T., Notomi, M., Abe, H., Natsume, M. and Kawaide, H. Arabidopsis CYP85A2 catalyzes lactonization reactions in the biosynthesis of 2-deoxy-7-oxalactone brassinosteroids. Biosci. Biotechnol. Biochem. 72 (2008) 2110–2117. [DOI] [PMID: 18685225]

[EC 1.14.14.180 created 2022]

1.14.14.181

Accepted name:

sulfoquinovose monooxygenase

Reaction:

6-sulfo-D-quinovose + FMNH₂ + O₂ = 6-dehydro-D-glucose + FMN + sulfite + H₂O

Glossary:

D-quinovose = 6-deoxy-D-glucopyranose
6-dehydro-D-glucose = 6-oxo-D-quinovose

Other name(s):

6-deoxy-6-sulfo-D-glucose monooxygenase; smoC (gene name); squD (gene name)

Systematic name:

6-sulfo-D-quinovose,FMNH₂:oxygen oxidoreductase

Comments:

The enzyme, characterized from the bacteria Agrobacterium fabrum and Rhizobium oryzae, is involved in a D-sulfoquinovose degradation pathway. FMNH₂ is provided by an associated FMN reductase [SmoA, EC 1.5.1.42, FMN reductase (NADH)].

Links to other databases:

References:

[EC 1.14.14.181 created 20022]

1.14.14.182

Accepted name:

taxoid 7β-hydroxylase

Reaction:

(1) taxusin + [reduced NADPH—hemoprotein reductase] + O₂ = 7β-hydroxytaxusin + [oxidized NADPH—hemoprotein reductase] + H₂O
(2) 2α-hydroxytaxusin + [reduced NADPH—hemoprotein reductase] + O₂ = 2α,7β-dihydroxytaxusin + [oxidized NADPH—hemoprotein reductase] + H₂O

Glossary:

taxusin = taxa-4(20),11-diene-5α,9α,10β,13α-tetrayl tetraacetate

Systematic name:

taxusin, [reduced NADPH—hemoprotein reductase]:oxygen 7-oxidoreductase

Comments:

A cytochrome P-450 (heme-thiolate) protein from the yew tree Taxus cuspidata. Does not act on earlier intermediates in taxol biosynthesis.

Links to other databases:

References:

1.	Chau, M., Jennewein, S., Walker, K. and Croteau, R. Taxol biosynthesis: Molecular cloning and characterization of a cytochrome P450 taxoid 7β-hydroxylase. Chem. Biol. 11 (2004) 663–672. [DOI] [PMID: 15157877]
2.	Chau, M. and Croteau, R. Molecular cloning and characterization of a cytochrome P450 taxoid 2α-hydroxylase involved in taxol biosynthesis. Arch. Biochem. Biophys. 427 (2004) 48–57. [DOI] [PMID: 15178487]

[EC 1.14.14.182 created 2012 as EC 1.14.13.147, transferred 2022 to EC 1.14.14.182]

1.14.14.183

Accepted name:

taxoid 2α-hydroxylase

Reaction:

(1) taxusin + [reduced NADPH—hemoprotein reductase] + O₂ = 2α-hydroxytaxusin + [oxidized NADPH—hemoprotein reductase] + H₂O
(2) 7β-hydroxytaxusin + [reduced NADPH—hemoprotein reductase] + O₂ = 2α,7β-dihydroxytaxusin + [oxidized NADPH—hemoprotein reductase] + H₂O

Glossary:

taxusin = taxa-4(20),11-diene-5α,9α,10β,13α-tetrayl tetraacetate

Systematic name:

taxusin, [reduced NADPH—hemoprotein reductase]:oxygen 2-oxidoreductase

Comments:

A cytochrome P-450 (heme-thiolate) protein from the yew tree Taxus cuspidata. Does not act on earlier intermediates in taxol biosynthesis.

Links to other databases:

References:

1.	Chau, M., Jennewein, S., Walker, K. and Croteau, R. Taxol biosynthesis: Molecular cloning and characterization of a cytochrome P450 taxoid 7β-hydroxylase. Chem. Biol. 11 (2004) 663–672. [DOI] [PMID: 15157877]
2.	Chau, M. and Croteau, R. Molecular cloning and characterization of a cytochrome P450 taxoid 2α-hydroxylase involved in taxol biosynthesis. Arch. Biochem. Biophys. 427 (2004) 48–57. [DOI] [PMID: 15178487]

[EC 1.14.14.183 created 2022]

1.14.99.51

Transferred entry:

hercynylcysteine S-oxide synthase, now listed as EC 1.21.3.10, hercynylcysteine S-oxide synthase.

[EC 1.14.99.51 created 2015, deleted 2021]

1.21.3.10

Accepted name:

hercynylcysteine S-oxide synthase

Reaction:

hercynine + L-cysteine + O₂ = S-(hercyn-2-yl)-L-cysteine S-oxide + H₂O

For diagram of ergothioneine and ovothiol biosynthesis, click here

Glossary:

hercynine = N^α,N^α,N^α-trimethyl-L-histidine

Other name(s):

Egt1; Egt-1

Systematic name:

hercynine,L-cysteine:oxygen [S-(hercyn-2-yl)-L-cysteine S-oxide-forming]

Comments:

Requires Fe²⁺ for activity. The enzyme, found in fungal species, is part of a fusion protein that also has the the activity of EC 2.1.1.44, L-histidine N^α-methyltransferase. It is part of the biosynthesis pathway of ergothioneine. The enzyme can also use L-selenocysteine to produce hercynylselenocysteine, which can be converted to selenoneine.

Links to other databases:

References:

1.	Pluskal, T., Ueno, M. and Yanagida, M. Genetic and metabolomic dissection of the ergothioneine and selenoneine biosynthetic pathway in the fission yeast, S. pombe, and construction of an overproduction system. PLoS One 9:e97774 (2014). [DOI] [PMID: 24828577]

[EC 1.21.3.10 created 2015 as 1.14.99.51, transferred 2022 to EC 1.21.3.10]

2.1.1.382

Accepted name:

methoxylated aromatic compound—corrinoid protein Co-methyltransferase

Reaction:

a methoxylated aromatic compound + a [Co(I) methoxylated-aromatic-compound-specific corrinoid protein] = a [methyl-Co(III) methoxylated-aromatic-compound-specific corrinoid protein] + a phenol

Other name(s):

mtoB (gene name); mtvB (gene name); vdmB (gene name)

Systematic name:

methoxylated aromatic compound:cobamide Co-methyltransferase

Comments:

This entry stands for a family of enzymes that have been characterized from acetogenic bacteria and archaeal species. Different members of this family have different substrate specificity. In the methanogenic archaeon Methermicoccus shengliensis the enzyme participates in methanogenesis from methoxylated aromatic compounds, while in acetogenic bacteria and in non-methanogenic archaea it participates in methoxydotrophic growth. Most of the enzymes have a wide specificity and were shown to act on a large number of methoxylated aromatic compounds, carrying a methoxy group at positions 2, 3 or 4 of the aromatic ring. Methylation of the corrinoid protein requires the central cobalt to be in the Co(I) state; during methylation the cobalt is oxidized to the Co(III) state.

Links to other databases:

References:

1.	Kaufmann, F., Wohlfarth, G. and Diekert, G. O-demethylase from Acetobacterium dehalogenans—substrate specificity and function of the participating proteins. Eur. J. Biochem. 253 (1998) 706–711. [DOI] [PMID: 9654069]
2.	Engelmann, T., Kaufmann, F. and Diekert, G. Isolation and characterization of a veratrol:corrinoid protein methyl transferase from Acetobacterium dehalogenans. Arch. Microbiol. 175 (2001) 376–383. [DOI] [PMID: 11409548]
3.	Naidu, D. and Ragsdale, S.W. Characterization of a three-component vanillate O-demethylase from Moorella thermoacetica. J. Bacteriol. 183 (2001) 3276–3281. [DOI] [PMID: 11344134]
4.	Pierce, E., Xie, G., Barabote, R.D., Saunders, E., Han, C.S., Detter, J.C., Richardson, P., Brettin, T.S., Das, A., Ljungdahl, L.G. and Ragsdale, S.W. The complete genome sequence of Moorella thermoacetica (f. Clostridium thermoaceticum). Environ. Microbiol. 10 (2008) 2550–2573. [DOI] [PMID: 18631365]
5.	Kurth, J.M., Nobu, M.K., Tamaki, H., de Jonge, N., Berger, S., Jetten, M.SM., Yamamoto, K., Mayumi, D., Sakata, S., Bai, L., Cheng, L., Nielsen, J.L., Kamagata, Y., Wagner, T. and Welte, C.U. Methanogenic archaea use a bacteria-like methyltransferase system to demethoxylate aromatic compounds. ISME J. 15 (2021) 3549–3565. [DOI] [PMID: 34145392]
6.	Welte, C.U., de Graaf, R., Dalcin Martins, P., Jansen, R.S., Jetten, M.SM. and Kurth, J.M. A novel methoxydotrophic metabolism discovered in the hyperthermophilic archaeon Archaeoglobus fulgidus. Environ. Microbiol. 23 (2021) 4017–4033. [DOI] [PMID: 33913565]

[EC 2.1.1.382 created 2022]

2.1.1.384

Accepted name:

[methyl-Co(III) methoxylated-aromatic-compound-specific corrinoid protein]—tetrahydromethanopterin methyltransferase

Reaction:

a [methyl-Co(III) methoxylated-aromatic-compound-specific corrinoid protein] + tetrahydromethanopterin = N⁵-methyltetrahydromethanopterin + a [Co(I) methoxylated-aromatic-compound-specific corrinoid protein]

Other name(s):

mtoA (gene name)

Systematic name:

[methylated methoxylated-aromatic-compound-specific corrinoid protein]:tetrahydromethanopterin methyltransferase

Comments:

The enzyme has been characterized from several archaeal species. In the methanogenic archaeon Methermicoccus shengliensis the enzyme participates in methanogenesis from methoxylated aromatic compounds, while in the non-methanogenic Archaeoglobus fulgidus it participates in methoxydotrophic growth. The enzyme catalyses the transfer of a methyl group bound to the cobalt cofactor of a dedicated corrinoid protein (MtoC) to tetrahydromethanopterin or tetrahydrosarcinapterin. cf. EC 2.1.1.385, [methyl-Co(III) methoxylated-aromatic-compound-specific corrinoid protein]—tetrahydrofolate methyltransferase.

Links to other databases:

References:

1.	Kurth, J.M., Nobu, M.K., Tamaki, H., de Jonge, N., Berger, S., Jetten, M.SM., Yamamoto, K., Mayumi, D., Sakata, S., Bai, L., Cheng, L., Nielsen, J.L., Kamagata, Y., Wagner, T. and Welte, C.U. Methanogenic archaea use a bacteria-like methyltransferase system to demethoxylate aromatic compounds. ISME J. 15 (2021) 3549–3565. [DOI] [PMID: 34145392]
2.	Welte, C.U., de Graaf, R., Dalcin Martins, P., Jansen, R.S., Jetten, M.SM. and Kurth, J.M. A novel methoxydotrophic metabolism discovered in the hyperthermophilic archaeon Archaeoglobus fulgidus. Environ. Microbiol. 23 (2021) 4017–4033. [DOI] [PMID: 33913565]

[EC 2.1.1.384 created 2022]

2.1.1.385

Accepted name:

[methyl-Co(III) methoxylated-aromatic-compound-specific corrinoid protein]—tetrahydrofolate methyltransferase

Reaction:

a [methyl-Co(III) methoxylated-aromatic-compound-specific corrinoid protein] + tetrahydrofolate = N⁵-methyltetrahydrofolate + a [Co(I) methoxylated-aromatic-compound-specific corrinoid protein]

Other name(s):

mtvA (gene name)

Systematic name:

[methylated methoxylated-aromatic-compound-specific corrinoid protein]:tetrahydrofolaten methyltransferase

Comments:

The enzyme, found in acetogenic bacteria, participates in a pathway for the degradation of methoxylated aromatic compounds (methoxydotrophic growth). The enzyme catalyses the transfer of a methyl group bound to the cobalt cofactor of a dedicated corrinoid protein (MtvC) to tetrahydrofolate. cf. EC 2.1.1.384, [methyl-Co(III) methoxylated-aromatic-compound-specific corrinoid protein]—tetrahydromethanopterin methyltransferase.

Links to other databases:

References:

1.	Kaufmann, F., Wohlfarth, G. and Diekert, G. O-demethylase from Acetobacterium dehalogenans—substrate specificity and function of the participating proteins. Eur. J. Biochem. 253 (1998) 706–711. [DOI] [PMID: 9654069]
2.	Naidu, D. and Ragsdale, S.W. Characterization of a three-component vanillate O-demethylase from Moorella thermoacetica. J. Bacteriol. 183 (2001) 3276–3281. [DOI] [PMID: 11344134]
3.	Pierce, E., Xie, G., Barabote, R.D., Saunders, E., Han, C.S., Detter, J.C., Richardson, P., Brettin, T.S., Das, A., Ljungdahl, L.G. and Ragsdale, S.W. The complete genome sequence of Moorella thermoacetica (f. Clostridium thermoaceticum). Environ. Microbiol. 10 (2008) 2550–2573. [DOI] [PMID: 18631365]

[EC 2.1.1.385 created 2022]

2.2.1.15

Accepted name:

6-deoxy-6-sulfo-D-fructose transketolase

Reaction:

(1) 6-deoxy-6-sulfo-D-fructose + D-glyceraldehyde-3-phosphate = D-xylulose-5-phosphate + 4-deoxy-4-sulfo-D-erythrose
(2) 4-deoxy-4-sulfo-D-erythrulose + D-glyceraldehyde-3-phosphate = D-xylulose-5-phosphate + sulfoacetaldehyde

Other name(s):

6-deoxy-6-sulfo-erythrulose transketolase; sqwGH (gene name)

Systematic name:

6-deoxy-6-sulfo-D-fructose:D-glyceraldehyde-3-phosphate glycolaldehydetransferase

Comments:

The enzyme, characterized from the bacterium Clostridium sp. MSTE9, is involved in a D-sulfoquinovose degradation pathway.

Links to other databases:

References:

1.	Liu, J., Wei, Y., Ma, K., An, J., Liu, X., Liu, Y., Ang, E.L., Zhao, H. and Zhang, Y. Mechanistically diverse pathways for sulfoquinovose degradation in bacteria. ACS Catal. 11 (2021) 14740–14750. [DOI]

[EC 2.2.1.15 created 2022]

2.3.1.309

Accepted name:

[β-tubulin]-L-lysine N-acetyltransferase

Reaction:

acetyl-CoA + a [β-tubulin]-L-lysine = CoA + a [β-tubulin]-N⁶-acetyl-L-lysine

Other name(s):

San; NatE; NAA50 (gene name)

Systematic name:

acetyl-CoA:[β-tubulin]-L-lysine N⁶-acetyltransferase

Comments:

The enzyme acetylates L-lysine at position 252 of β-tubulin, which is located at the interface of α/β-tubulin heterodimers and interacts with the phosphate group of the α-tubulin-bound GTP. The acetylation is thought to attenuate tubulin incorporation into microtubules. The enzyme catalysing this activity (NAA50) also catalyses the acetylation of certain N-terminal methionyl residues. That activity is classified as EC 2.3.1.258, N-terminal methionine N^α-acetyltransferase NatE. cf. EC 2.3.1.108, α-tubulin N-acetyltransferase.

Links to other databases:

References:

1.	Chu, C.W., Hou, F., Zhang, J., Phu, L., Loktev, A.V., Kirkpatrick, D.S., Jackson, P.K., Zhao, Y. and Zou, H. A novel acetylation of β-tubulin by San modulates microtubule polymerization via down-regulating tubulin incorporation. Mol. Biol. Cell 22 (2011) 448–456. [DOI] [PMID: 21177827]

[EC 2.3.1.309 created 2022]

2.3.1.310

Accepted name:

benzoylsuccinyl-CoA thiolase

Reaction:

(S)-2-benzoylsuccinyl-CoA + CoA = benzoyl-CoA + succinyl-CoA

Other name(s):

bbsAB (gene names)

Systematic name:

(S)-2-benzoylsuccinyl-CoA:CoA benzoyltransferase (benzoyl-CoA-forming)

Comments:

The enzyme, characterized from the bacteria Thauera aromatica and Geobacter metallireducens, participates in an anaerobic toluene degradation pathway.

Links to other databases:

References:

1.	Leuthner, B. and Heider, J. Anaerobic toluene catabolism of Thauera aromatica: the bbs operon codes for enzymes of β oxidation of the intermediate benzylsuccinate. J. Bacteriol. 182 (2000) 272–277. [DOI] [PMID: 10629170]
2.	Weidenweber, S., Schuhle, K., Lippert, M.L., Mock, J., Seubert, A., Demmer, U., Ermler, U. and Heider, J. Finis tolueni: a new type of thiolase with an integrated Zn-finger subunit catalyzes the final step of anaerobic toluene metabolism. FEBS J. (2022) . [DOI] [PMID: 35313080]

[EC 2.3.1.310 created 2022]

*EC

2.4.1.110

Accepted name:

tRNA-queuosine α-mannosyltransferase

Reaction:

GDP-α-D-mannose + queuosine³⁴ in tRNA^Asp = GDP + O-4′′-α-D-mannosylqueuosine³⁴ in tRNA^Asp

Other name(s):

GDP-mannose:tRNA^Asp-queuosine O-5′′-β-D-mannosyltransferase (incorrect); tRNA-queuosine β-mannosyltransferase (incorrect)

Systematic name:

GDP-α-D-mannose:queuosine³⁴ in tRNA^Asp O-4′′-α-D-mannosyltransferase (configuration-retaining)

Comments:

This enzyme, found in higher vertebrates, modifies tRNA^Asp at the wobble position of the anticodon loop.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 9055-06-5

References:

1.	Okada, N. and Nishimura, S. Enzymatic synthesis of Q nucleoside containing mannose in the anticodon of tRNA: isolation of a novel mannosyltransferase from a cell-free extract of rat liver. Nucleic Acids Res. 4 (1977) 2931–2938. [DOI] [PMID: 20603]
2.	Hillmeier, M., Wagner, M., Ensfelder, T., Korytiakova, E., Thumbs, P., Muller, M. and Carell, T. Synthesis and structure elucidation of the human tRNA nucleoside mannosyl-queuosine. Nat. Commun. 12:7123 (2021). [DOI] [PMID: 34880214]

[EC 2.4.1.110 created 1984, modified 2022]

*EC

2.4.1.221

Accepted name:

peptide-O-fucosyltransferase

Reaction:

GDP-β-L-fucose + [protein]-(L-serine/L-threonine) = GDP + [protein]-3-O-(α-L-fucosyl)-(L-serine/L-threonine)

Other name(s):

GDP-L-fucose:polypeptide fucosyltransferase; GDP-fucose protein O-fucosyltransferase; GDP-fucose:polypeptide fucosyltransferase; POFUT1 (gene name); POFUT2 (gene name)

Systematic name:

GDP-β-L-fucose:protein-(L-serine/L-threonine) O-α-L-fucosyltransferase (configuration-inverting)

Comments:

The enzyme, found in animals and plants, is involved in the biosynthesis of O-fucosylated proteins. In EGF domains, the attachment of O-linked fucose to serine or threonine occurs within the sequence Cys-Xaa-Xaa-Gly-Gly-Ser^/Thr-Cys.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9033-08-3

References:

1.	Wang, Y. and Spellman, M.W. Purification and characterization of a GDP-fucose:polypeptide fucosyltransferase from Chinese hamster ovary cells. J. Biol. Chem. 273 (1998) 8112–8118. [DOI] [PMID: 9525914]
2.	Wang, Y., Shao, L., Shi, S., Harris, R.J., Spellman, M.W., Stanley, P. and Haltiwanger, R.S. Modification of epidermal growth factor-like repeats with O-fucose. Molecular cloning and expression of a novel GDP-fucose protein O-fucosyltransferase. J. Biol. Chem. 276 (2001) 40338–40345. [DOI] [PMID: 11524432]
3.	Wang, Y., Lee, G.F., Kelley, R.F. and Spellman, M.W. Identification of a GDP-L-fucose:polypeptide fucosyltransferase and enzymatic addition of O-linked fucose to EGF domains. Glycobiology 6 (1996) 837–842. [DOI] [PMID: 9023546]
4.	Hofsteenge, J., Huwiler, K.G., Macek, B., Hess, D., Lawler, J., Mosher, D.F. and Peter-Katalinic, J. C-Mannosylation and O-fucosylation of the thrombospondin type 1 module. J. Biol. Chem. 276 (2001) 6485–6498. [DOI] [PMID: 11067851]
5.	Valero-Gonzalez, J., Leonhard-Melief, C., Lira-Navarrete, E., Jimenez-Oses, G., Hernandez-Ruiz, C., Pallares, M.C., Yruela, I., Vasudevan, D., Lostao, A., Corzana, F., Takeuchi, H., Haltiwanger, R.S. and Hurtado-Guerrero, R. A proactive role of water molecules in acceptor recognition by protein O-fucosyltransferase 2. Nat. Chem. Biol. 12 (2016) 240–246. [DOI] [PMID: 26854667]
6.	Zentella, R., Sui, N., Barnhill, B., Hsieh, W.P., Hu, J., Shabanowitz, J., Boyce, M., Olszewski, N.E., Zhou, P., Hunt, D.F. and Sun, T.P. The Arabidopsis O-fucosyltransferase SPINDLY activates nuclear growth repressor DELLA. Nat. Chem. Biol. 13 (2017) 479–485. [DOI] [PMID: 28244988]
7.	Lopaticki, S., Yang, A.SP., John, A., Scott, N.E., Lingford, J.P., O'Neill, M.T., Erickson, S.M., McKenzie, N.C., Jennison, C., Whitehead, L.W., Douglas, D.N., Kneteman, N.M., Goddard-Borger, E.D. and Boddey, J.A. Protein O-fucosylation in Plasmodium falciparum ensures efficient infection of mosquito and vertebrate hosts. Nat. Commun. 8:561 (2017). [DOI] [PMID: 28916755]

[EC 2.4.1.221 created 2002, modified 2022]

*EC

2.4.1.222

Accepted name:

O-fucosylpeptide 3-β-N-acetylglucosaminyltransferase

Reaction:

UDP-N-acetyl-α-D-glucosamine + [protein with EGF-like domain]-3-O-(α-L-fucosyl)-(L-serine/L-threonine) = UDP + [protein with EGF-like domain]-3-O-[N-acetyl-β-D-glucosaminyl-(1→3)-α-L-fucosyl]-(L-serine/L-threonine)

Glossary:

EGF = epidermal growth factor
EGF-like domain = an evolutionary conserved domain containing 30 to 40 amino-acid residues first described from epidermal growth factor

Other name(s):

O-fucosylpeptide β-1,3-N-acetylglucosaminyltransferase; fringe; UDP-D-GlcNAc:O-L-fucosylpeptide 3-β-N-acetyl-D-glucosaminyltransferase

Systematic name:

UDP-N-acetyl-α-D-glucosamine:[protein with EGF-like domain]-3-O-(α-L-fucosyl)-(L-serine/L-threonine) 3-β-N-acetyl-D-glucosaminyltransferase (configuration-inverting)

Comments:

The enzyme, found in animals and plants, is involved in the biosynthesis of the tetrasaccharides α-Neu5Ac-(2→3)-β-D-Gal-(1→4)-β-D-GlcNAc-(1→3)-α-L-Fuc and α-Neu5Ac-(2→6)-β-D-Gal-(1→4)-β-D-GlcNAc-(1→3)-α-L-Fuc, which are attached to L-Ser or L-Thr residues within the sequence Cys-Xaa-Xaa-Gly-Gly-Ser^/Thr-Cys in EGF-like domains in Notch and Factor-X proteins, respectively. The substrate is provided by EC 2.4.1.221, peptide-O-fucosyltransferase.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 299203-70-6

References:

1.	Moloney, D.J., Panin, V.M., Johnston, S.H., Chen, J., Shao, L., Wilson, R., Wang, Y., Stanley, P., Irvine, K.D., Haltiwanger, R.S. and Vogt, T.F. Fringe is a glycosyltransferase that modifies Notch. Nature 406 (2000) 369–375. [DOI] [PMID: 10935626]
2.	Bruckner, K., Perez, L., Clausen, H. and Cohen, S. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions. Nature 406 (2000) 411–415. [DOI] [PMID: 10935637]
3.	Rampal, R., Li, A.S., Moloney, D.J., Georgiou, S.A., Luther, K.B., Nita-Lazar, A. and Haltiwanger, R.S. Lunatic fringe, manic fringe, and radical fringe recognize similar specificity determinants in O-fucosylated epidermal growth factor-like repeats. J. Biol. Chem. 280 (2005) 42454–42463. [DOI] [PMID: 16221665]

[EC 2.4.1.222 created 2002, modified 2022]

2.4.1.389

Accepted name:

solabiose phosphorylase

Reaction:

solabiose + phosphate = D-galactose + α-D-glucose 1-phosphate

Glossary:

solabiose = β-D-glucopyranosyl-(1→3)-D-galactose

Systematic name:

solabiose:phosphate α-D-glucosyltransferase

Comments:

The enzyme, characterized from the bacterium Paenibacillus borealis, belongs to glycoside hydrolase family 94 (GH94).

Links to other databases:

References:

1.	Saburi, W., Nihira, T., Nakai, H., Kitaoka, M. and Mori, H. Discovery of solabiose phosphorylase and its application for enzymatic synthesis of solabiose from sucrose and lactose. Sci. Rep. 12:259 (2022). [DOI] [PMID: 34997180]

[EC 2.4.1.389 created 2022]

2.4.99.23

Accepted name:

lipopolysaccharide heptosyltransferase I

Reaction:

ADP-L-glycero-β-D-manno-heptose + an α-Kdo-(2→4)-α-Kdo-(2→6)-[lipid A] = ADP + an α-Hep-(1→5)-[α-Kdo-(2→4)]-α-Kdo-(2→6)-[lipid A]

Glossary:

Lipid A is a lipid component of the lipopolysaccharides (LPS) of Gram-negative bacteria. It consists of two glucosamine units connected by a β(1→6) bond and decorated with four to seven acyl chains and up to two phosphate groups.
Hep = L-glycero-D-manno-heptose

Other name(s):

HepI; rfaC (gene name); WaaC; heptosyltransferase I (ambiguous)

Systematic name:

ADP-L-glycero-β-D-manno-heptose:an α-Kdo-(2→4)-α-Kdo-(2→6)-[lipid A] 5-α-heptosyltransferase

Comments:

The enzyme catalyses a glycosylation step in the biosynthesis of the inner core oligosaccharide of the lipopolysaccharide (endotoxin) of many Gram-negative bacteria.

Links to other databases:

References:

1.	Kadrmas, J.L. and Raetz, C.R. Enzymatic synthesis of lipopolysaccharide in Escherichia coli. Purification and properties of heptosyltransferase i. J. Biol. Chem. 273 (1998) 2799–2807. [DOI] [PMID: 9446588]
2.	de Kievit, T.R. and Lam, J.S. Isolation and characterization of two genes, waaC (rfaC) and waaF (rfaF), involved in Pseudomonas aeruginosa serotype O5 inner-core biosynthesis. J. Bacteriol. 179 (1997) 3451–3457. [DOI] [PMID: 9171387]
3.	Klena, J.D., Gray, S.A. and Konkel, M.E. Cloning, sequencing, and characterization of the lipopolysaccharide biosynthetic enzyme heptosyltransferase I gene (waaC) from Campylobacter jejuni and Campylobacter coli. Gene 222 (1998) 177–185. [DOI] [PMID: 9831648]
4.	Gronow, S., Oertelt, C., Ervela, E., Zamyatina, A., Kosma, P., Skurnik, M. and Holst, O. Characterization of the physiological substrate for lipopolysaccharide heptosyltransferases I and II. J Endotoxin Res 7 (2001) 263–270. [PMID: 11717579]
5.	Grizot, S., Salem, M., Vongsouthi, V., Durand, L., Moreau, F., Dohi, H., Vincent, S., Escaich, S. and Ducruix, A. Structure of the Escherichia coli heptosyltransferase WaaC: binary complexes with ADP and ADP-2-deoxy-2-fluoro heptose. J. Mol. Biol. 363 (2006) 383–394. [DOI] [PMID: 16963083]

[EC 2.4.99.23 created 2022]

2.4.99.24

Accepted name:

lipopolysaccharide heptosyltransferase II

Reaction:

ADP-L-glycero-β-D-manno-heptose + an α-Hep-(1→5)-[α-Kdo-(2→4)]-α-Kdo-(2→6)-[lipid A] = ADP + an α-Hep-(1→3)-α-Hep-(1→5)-[α-Kdo-(2→4)]-α-Kdo-(2→6)-[lipid A]

Glossary:

Other name(s):

HepII; rfaF (gene name); WaaF; heptosyltransferase II

Systematic name:

ADP-L-glycero-β-D-manno-heptose:an α-L-glycero-D-manno-heptosyl-(1→5)-[α-Kdo-(2→4)]-α -Kdo-(2→6)-[lipid A] 3-α-heptosyltransferase

Comments:

The enzyme catalyses a glycosylation step in the biosynthesis of the inner core oligosaccharide of the lipopolysaccharide (endotoxin) of some Gram-negative bacteria.

Links to other databases:

References:

1.	Allen, A.G., Isobe, T. and Maskell, D.J. Identification and cloning of waaF (rfaF) from Bordetella pertussis and use to generate mutants of Bordetella spp. with deep rough lipopolysaccharide. J. Bacteriol. 180 (1998) 35–40. [DOI] [PMID: 9422589]
2.	Bauer, B.A., Lumbley, S.R. and Hansen, E.J. Characterization of a WaaF (RfaF) homolog expressed by Haemophilus ducreyi. Infect. Immun. 67 (1999) 899–907. [DOI] [PMID: 9916106]
3.	Gronow, S., Brabetz, W. and Brade, H. Comparative functional characterization in vitro of heptosyltransferase I (WaaC) and II (WaaF) from Escherichia coli. Eur. J. Biochem. 267 (2000) 6602–6611. [DOI] [PMID: 11054112]
4.	Gronow, S., Oertelt, C., Ervela, E., Zamyatina, A., Kosma, P., Skurnik, M. and Holst, O. Characterization of the physiological substrate for lipopolysaccharide heptosyltransferases I and II. J Endotoxin Res 7 (2001) 263–270. [PMID: 11717579]
5.	Oldfield, N.J., Moran, A.P., Millar, L.A., Prendergast, M.M. and Ketley, J.M. Characterization of the Campylobacter jejuni heptosyltransferase II gene, waaF, provides genetic evidence that extracellular polysaccharide is lipid A core independent. J. Bacteriol. 184 (2002) 2100–2107. [DOI] [PMID: 11914340]

[EC 2.4.99.24 created 2022]

2.4.99.25

Accepted name:

lipopolysaccharide heptosyltransferase III

Reaction:

ADP-L-glycero-β-D-manno-heptose + an α-Hep-(1→3)-4-O-phospho-α-Hep-(1→5)-[α-Kdo-(2→4)]-α-Kdo-(2→6)-[lipid A] = ADP + an α-Hep-(1→7)-α-Hep-(1→3)-4-O-phospho-α-Hep-(1→5)-[α-Kdo-(2→4)]-α-Kdo-(2→6)-[lipid A]

Glossary:

Other name(s):

waaQ (gene name); rfaQ (gene name)

Systematic name:

ADP-L-glycero-β-D-manno-heptose:an α-Hep-(1→3)-4-O-phospho-α-Hep-(1→5)-[α-Kdo-(2→4)]-α-Kdo-(2→6)-[lipid A] heptose^I 7-α-heptosyltransferase

Comments:

The enzyme catalyses a glycosylation step in the biosynthesis of the inner core oligosaccharide of the lipopolysaccharide (endotoxin) of some Gram-negative bacteria.

Links to other databases:

References:

1.	Mudapaka, J. and Taylor, E.A. Cloning and characterization of the Escherichia coli heptosyltransferase III: Exploring substrate specificity in lipopolysaccharide core biosynthesis. FEBS Lett. 589 (2015) 1423–1429. [DOI] [PMID: 25957775]

[EC 2.4.99.25 created 2022]

2.5.1.155

Accepted name:

phosphoglycerol geranylfarnesyltransferase

Reaction:

all-trans-pentaprenyl diphosphate + sn-glycerol 1-phosphate = sn-3-O-(farnesylgeranyl)glycerol 1-phosphate + diphosphate

Other name(s):

GFGP synthase

Systematic name:

all-trans pentaprenyl diphosphate:sn-glycerol-1-phosphate pentaprenyltransferase

Comments:

The enzyme, characterized from the archaeon Aeropyrum pernix, catalyses the first pathway-specific step in the biosynthesis of the core membrane C₂₅,C₂₅-diether lipids in some archaea. It does not act on geranylgeranyl diphosphate. cf. EC 2.5.1.41, phosphoglycerol geranylgeranyltransferase.

Links to other databases:

References:

1.	Yoshida, R., Yoshimura, T. and Hemmi, H. Biosynthetic machinery for C₂₅,C₂₅-diether archaeal lipids from the hyperthermophilic archaeon Aeropyrum pernix. Biochem. Biophys. Res. Commun. 497 (2018) 87–92. [DOI] [PMID: 29427665]

[EC 2.5.1.155 created 2022]

2.5.1.156

Accepted name:

geranylfarnesylglycerol-phosphate geranylfarnesyltransferase

Reaction:

all-trans-pentaprenyl diphosphate + sn-3-O-(farnesylgeranyl)glycerol 1-phosphate = 2,3-bis-O-(geranylfarnesyl)-sn-glycerol 1-phosphate + diphosphate

Other name(s):

DGFGP synthase; 2,3-bis-O-(farnesylgeranyl)-sn-glycerol 1-phosphate synthase; 2,3-di-O-farnesylgeranylglyceryl synthase

Systematic name:

all-trans-pentaprenyl diphosphate:sn-3-O-(pentaprenyl)glycerol 1-phosphate pentaprenyltransferase

Comments:

The enzyme, characterized from the archaeon Aeropyrum pernix, carries out the second prenyltransfer reaction involved in the formation of C₂₅,C₂₅ membrane diether-lipids in some archaea. Requires a divalent metal cation, such as Mg²⁺. The enzyme cannot accept sn-3-(O-geranylgeranyl)glycerol 1-phosphate as the prenyl donor. cf. EC 2.5.1.42, geranylgeranylglycerol-phosphate geranylgeranyltransferase.

Links to other databases:

References:

1.	Yoshida, R., Yoshimura, T. and Hemmi, H. Biosynthetic machinery for C₂₅,C₂₅-diether archaeal lipids from the hyperthermophilic archaeon Aeropyrum pernix. Biochem. Biophys. Res. Commun. 497 (2018) 87–92. [DOI] [PMID: 29427665]

[EC 2.5.1.156 created 2022]

2.6.1.124

Accepted name:

[amino-group carrier protein]-γ-(L-ornithyl)-L-glutamate aminotransferase

Reaction:

an [amino-group carrier protein]-C-terminal-[γ-(L-ornithyl)-L-glutamate] + 2-oxoglutarate = an [amino-group carrier protein]-C-terminal-[γ-(L-glutamate 5-semialdehyde-2-yl)-L-glutamate] + L-glutamate

Other name(s):

lysJ (gene name)

Systematic name:

2-oxoglutarate:[amino-group carrier protein]-C-terminal-[γ-(L-ornithyl)-L-glutamate] aminotransferase

Comments:

The enzyme participates in an L-arginine biosynthetic pathway that operates in certain species of archaea. In some cases the enzyme also catalyses the activity of EC 2.6.1.118, [amino-group carrier protein]-γ-(L-lysyl)-L-glutamate aminotransferase.

Links to other databases:

References:

1.	Yoshida, A., Tomita, T., Atomi, H., Kuzuyama, T. and Nishiyama, M. Lysine biosynthesis of Thermococcus kodakarensis with the capacity to function as an ornithine biosynthetic system. J. Biol. Chem. 291 (2016) 21630–21643. [DOI] [PMID: 27566549]

[EC 2.6.1.124 created 2022]

2.7.1.237

Accepted name:

GTP-dependent dephospho-CoA kinase

Reaction:

GTP + 3′-dephospho-CoA = GDP + CoA

Systematic name:

GTP:3′-dephospho-CoA 3′-phosphotransferase

Comments:

The enzyme, characterized from the archaeon Thermococcus kodakarensis, participates in a coenzyme A biosynthesis pathway. cf. EC 2.7.1.24, dephospho-CoA kinase.

Links to other databases:

BRENDA, EXPASY, GTD, KEGG, PDB

References:

1.	Shimosaka, T., Makarova, K.S., Koonin, E.V. and Atomi, H. Identification of dephospho-coenzyme A (dephospho-CoA) kinase in Thermococcus kodakarensis and elucidation of the entire CoA biosynthesis pathway in archaea. mBio 10 (2019) . [DOI] [PMID: 31337720]

[EC 2.7.1.237 created 2022]

2.7.1.238

Accepted name:

phenol phosphorylase

Reaction:

ATP + phenol + H₂O = AMP + phenyl phosphate + phosphate

Other name(s):

phenylphosphate synthase

Systematic name:

ATP:phenol phosphotransferase (AMP-forming)

Comments:

The enzyme, characterized from the bacterium Thauera aromatica, catalyses the first step in an anaerobic phenol degradation pathway. The enzyme, composed of three subunits, transfers the β-phosphoryl from ATP to phenol, forming phenyl phosphate, AMP, and phosphate [1]. During catalysis a diphosphoryl group is transferred from ATP to a histidine residue in one of the enzyme's subunits, from which phosphate is cleaved to render the reaction unidirectional. The remaining histidine phosphate subsequently serves as the actual phosphorylation agent [2].

Links to other databases:

References:

1.	Schmeling, S., Narmandakh, A., Schmitt, O., Gad'on, N., Schuhle, K. and Fuchs, G. Phenylphosphate synthase: a new phosphotransferase catalyzing the first step in anaerobic phenol metabolism in Thauera aromatica. J. Bacteriol. 186 (2004) 8044–8057. [DOI] [PMID: 15547277]
2.	Narmandakh, A., Gad'on, N., Drepper, F., Knapp, B., Haehnel, W. and Fuchs, G. Phosphorylation of phenol by phenylphosphate synthase: role of histidine phosphate in catalysis. J. Bacteriol. 188 (2006) 7815–7822. [DOI] [PMID: 16980461]

[EC 2.7.1.238 created 2022]

2.7.2.19

Accepted name:

[amino-group carrier protein]-L-glutamate 6-kinase

Reaction:

ATP + an [amino-group carrier protein]-C-terminal-γ-(L-glutamyl)-L-glutamate = ADP + an [amino-group carrier protein]-C-terminal-γ-(5-phospho-L-glutamyl)-L-glutamate

Other name(s):

lysZ (gene name)

Systematic name:

[amino-group carrier protein]-C-terminal-γ-(L-glutamyl)-L-glutamine 5-O-kinase

Comments:

The enzyme participates in an L-arginine biosynthetic pathway in certain species of archaea. In some organisms the enzyme also catalyses the activity of EC 2.7.2.17, [amino-group carrier protein]-L-2-aminoadipate 6-kinase.

Links to other databases:

References:

1.	Ouchi, T., Tomita, T., Horie, A., Yoshida, A., Takahashi, K., Nishida, H., Lassak, K., Taka, H., Mineki, R., Fujimura, T., Kosono, S., Nishiyama, C., Masui, R., Kuramitsu, S., Albers, S.V., Kuzuyama, T. and Nishiyama, M. Lysine and arginine biosyntheses mediated by a common carrier protein in Sulfolobus. Nat. Chem. Biol. 9 (2013) 277–283. [DOI] [PMID: 23434852]
2.	Yoshida, A., Tomita, T., Atomi, H., Kuzuyama, T. and Nishiyama, M. Lysine biosynthesis of Thermococcus kodakarensis with the capacity to function as an ornithine biosynthetic system. J. Biol. Chem. 291 (2016) 21630–21643. [DOI] [PMID: 27566549]

[EC 2.7.2.19 created 2022]

*EC

2.7.4.21

Accepted name:

inositol-hexakisphosphate 5-kinase

Reaction:

(1) ATP + 1D-myo-inositol hexakisphosphate = ADP + 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate
(2) ATP + 1D-myo-inositol 1-diphosphate 2,3,4,5,6-pentakisphosphate = ADP + 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate

Other name(s):

ATP:1D-myo-inositol-hexakisphosphate phosphotransferase; IP6K; inositol-hexakisphosphate kinase (ambiguous)

Systematic name:

ATP:1D-myo-inositol-hexakisphosphate 5-phosphotransferase

Comments:

Three mammalian isoforms are known to exist.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 176898-37-6

References:

1.	Saiardi, A., Erdjument-Bromage, H., Snowman, A.M., Tempst, P. and Snyder, S.H. Synthesis of diphosphoinositol pentakisphosphate by a newly identified family of higher inositol polyphosphate kinases. Curr. Biol. 9 (1999) 1323–1326. [DOI] [PMID: 10574768]
2.	Schell, M.J., Letcher, A.J., Brearley, C.A., Biber, J., Murer, H. and Irvine, R.F. PiUS (P_i uptake stimulator) is an inositol hexakisphosphate kinase. FEBS Lett. 461 (1999) 169–172. [DOI] [PMID: 10567691]
3.	Albert, C., Safrany, S.T., Bembenek, M.E., Reddy, K.M., Reddy, K.K., Falck, J.-R., Bröcker, M., Shears, S.B. and Mayr, G.W. Biological variability in the structures of diphosphoinositol polyphosphates in Dictyostelium discoideum and mammalian cells. Biochem. J. 327 (1997) 553–560. [DOI] [PMID: 9359429]
4.	Lin, H., Fridy, P.C., Ribeiro, A.A., Choi, J.H., Barma, D.K., Vogel, G., Falck, J.R., Shears, S.B., York, J.D. and Mayr, G.W. Structural analysis and detection of biological inositol pyrophosphates reveal that the family of VIP/diphosphoinositol pentakisphosphate kinases are 1/3-kinases. J. Biol. Chem. 284 (2009) 1863–1872. [DOI] [PMID: 18981179]
5.	Wang, H., Falck, J.R., Hall, T.M. and Shears, S.B. Structural basis for an inositol pyrophosphate kinase surmounting phosphate crowding. Nat. Chem. Biol. 8 (2012) 111–116. [DOI] [PMID: 22119861]

[EC 2.7.4.21 created 2002 as EC 2.7.1.152, transferred 2003 to EC 2.7.4.21, modified 2013, modified 2022]

*EC

2.7.4.24

Accepted name:

diphosphoinositol-pentakisphosphate 1-kinase

Reaction:

(1) ATP + 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate = ADP + 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate
(2) ATP + 1D-myo-inositol hexakisphosphate = ADP + 1D-myo-inositol 1-diphosphate 2,3,4,5,6-pentakisphosphate

Other name(s):

PP-IP₅ kinase; diphosphoinositol pentakisphosphate kinase; ATP:5-diphospho-1D-myo-inositol-pentakisphosphate phosphotransferase; PP-InsP₅ kinase; PPIP5K; PPIP5K1; PPIP5K2; VIP1; VIP2; diphosphoinositol-pentakisphosphate 1/3-kinase (incorrect); diphosphoinositol-pentakisphosphate kinase (ambiguous)

Systematic name:

ATP:1D-myo-inositol-5-diphosphate-pentakisphosphate 1-phosphotransferase

Comments:

This enzyme is activated by osmotic shock [4]. Ins(1,3,4,5,6)P₅, 1D-myo-inositol diphosphate tetrakisphosphate and 1D-myo-inositol bisdiphosphate triphosphate are not substrates [4]. The enzyme specifically phosphorylates the 1-position of the substrates [6].

Links to other databases:

References:

1.	Shears, S.B., Ali, N., Craxton, A. and Bembenek, M.E. Synthesis and metabolism of bis-diphosphoinositol tetrakisphosphate in vitro and in vivo. J. Biol. Chem. 270 (1995) 10489–10497. [DOI] [PMID: 7737983]
2.	Albert, C., Safrany, S.T., Bembenek, M.E., Reddy, K.M., Reddy, K.K., Falck, J.-R., Bröcker, M., Shears, S.B. and Mayr, G.W. Biological variability in the structures of diphosphoinositol polyphosphates in Dictyostelium discoideum and mammalian cells. Biochem. J. 327 (1997) 553–560. [DOI] [PMID: 9359429]
3.	Fridy, P.C., Otto, J.C., Dollins, D.E. and York, J.D. Cloning and characterization of two human VIP1-like inositol hexakisphosphate and diphosphoinositol pentakisphosphate kinases. J. Biol. Chem. 282 (2007) 30754–30762. [DOI] [PMID: 17690096]
4.	Choi, J.H., Williams, J., Cho, J., Falck, J.R. and Shears, S.B. Purification, sequencing, and molecular identification of a mammalian PP-InsP₅ kinase that Is activated when cells are exposed to hyperosmotic stress. J. Biol. Chem. 282 (2007) 30763–30775. [DOI] [PMID: 17702752]
5.	Lin, H., Fridy, P.C., Ribeiro, A.A., Choi, J.H., Barma, D.K., Vogel, G., Falck, J.R., Shears, S.B., York, J.D. and Mayr, G.W. Structural analysis and detection of biological inositol pyrophosphates reveal that the family of VIP/diphosphoinositol pentakisphosphate kinases are 1/3-kinases. J. Biol. Chem. 284 (2009) 1863–1872. [DOI] [PMID: 18981179]
6.	Wang, H., Falck, J.R., Hall, T.M. and Shears, S.B. Structural basis for an inositol pyrophosphate kinase surmounting phosphate crowding. Nat. Chem. Biol. 8 (2012) 111–116. [DOI] [PMID: 22119861]

[EC 2.7.4.24 created 2003 as EC 2.7.1.155, transferred 2007 to EC 2.7.4.24, modified 2014, modified 2022]

2.7.7.108

Accepted name:

protein adenylyltransferase

Reaction:

(1) ATP + a [protein]-L-serine = diphosphate + a [protein]-O-(5′-adenylyl)-L-serine
(1) ATP + a [protein]-L-threonine = diphosphate + a [protein]-O-(5′-adenylyl)-L-threonine
(1) ATP + a [protein]-L-tyrosine = diphosphate + a [protein]-O-(5′-adenylyl)-L-tyrosine

Other name(s):

AMPylase; selO (gene name); FMP40 (gene name); SELENOO (gene name); IbpA; VopS; DrrA; FICD (gene name)

Systematic name:

[protein] L-serine/L-threonine/L-tyrosine adenylyltransferase

Comments:

The enzyme, commonly referred to as AMPylase, transfers an adenylyl (adenosine 5′-phosphate) group from ATP to L-serine, L-threonine, and L-tyrosine residues in its target protein substrates. AMPylation is found in both prokaryotes and eukaryotes. In bacteria AMPylases are abundant enzymes that either regulate the function of endogenous bacterial proteins or are translocated into host cells to hijack host cell signalling processes. Metazoans AMPylases are either enzymes containing a conserved Fic domain that primarily modify the ER-resident chaperone BiP, or mitochondrial selenocysteine-containing proteins (SelO) involved in redox signalling.

Links to other databases:

References:

1.	Xiao, J., Worby, C.A., Mattoo, S., Sankaran, B. and Dixon, J.E. Structural basis of Fic-mediated adenylylation. Nat. Struct. Mol. Biol. 17 (2010) 1004–1010. [DOI] [PMID: 20622875]
2.	Palanivelu, D.V., Goepfert, A., Meury, M., Guye, P., Dehio, C. and Schirmer, T. Fic domain-catalyzed adenylylation: insight provided by the structural analysis of the type IV secretion system effector BepA. Protein Sci. 20 (2011) 492–499. [DOI] [PMID: 21213248]
3.	Truttmann, M.C., Cruz, V.E., Guo, X., Engert, C., Schwartz, T.U. and Ploegh, H.L. The Caenorhabditis elegans protein FIC-1 is an AMPylase that covalently modifies heat-shock 70 family proteins, translation elongation factors and histones. PLoS Genet. 12:e1006023 (2016). [DOI] [PMID: 27138431]
4.	Sreelatha, A., Yee, S.S., Lopez, V.A., Park, B.C., Kinch, L.N., Pilch, S., Servage, K.A., Zhang, J., Jiou, J., Karasiewicz-Urbanska, M., Lobocka, M., Grishin, N.V., Orth, K., Kucharczyk, R., Pawlowski, K., Tomchick, D.R. and Tagliabracci, V.S. Protein AMPylation by an evolutionarily conserved pseudokinase. Cell 175 (2018) 809–821. [DOI] [PMID: 30270044]
5.	Bardwell, L. Pseudokinases: Flipping the ATP for AMPylation. Curr. Biol. 29 (2019) R23–R25. [DOI] [PMID: 30620911]
6.	Chatterjee, B.K. and Truttmann, M.C. Fic and non-Fic AMPylases: protein AMPylation in metazoans. Open Biol 11:210009 (2021). [DOI] [PMID: 33947243]

[EC 2.7.7.108 created 2022]

*EC

2.7.11.11

Accepted name:

cAMP-dependent protein kinase

Reaction:

ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate

Glossary:

3′,5′-cyclic-AMP = cAMP

Other name(s):

PKA; protein kinase A; PKA catalytic (C) subunit; A kinase; ATP:protein phosphotransferase (cAMP-dependent)

Systematic name:

ATP:protein Ser^/Thr-phosphotransferase (3′,5′-cAMP-dependent)

Comments:

This eukaryotic enzyme recognizes the sequence -Arg-Arg-X-Ser*/Thr*-Hpo, where * indicates the phosphorylated residue and Hpo indicates a hydrophobic residue.The inactive holoenzyme is a heterotetramer composed of two regulatory (R) subunits and two catalytic (C) subunits. Each R subunit occludes the active site of a C subunit and contains two binding sites for 3′,5′-cyclic-AMP (cAMP). Binding of cAMP activates the enzyme by causing conformational changes that release two free monomeric C subunits from a dimer of the R subunits, i.e. R2C2 + 4 cAMP = R2(cAMP)4 + 2 C. Activity requires phosphorylation of a conserved Thr in the activation loop (T-loop) sequence (Thr¹⁹⁸ in human Cα; Thr²²⁴ in budding yeast Tpk2), installed by auto-phosphorylation or by the 3-phosphoinositide-dependent protein kinase-1 (PDPK1). Certain R2C2 combinations can be localized to particular subcellular regions by their association with diverse species of 'A Kinase-Anchoring Proteins' (AKAPs). The enzyme has been characterized from many organisms. Humans have three C units (Cα, Cβ, and Cγ) encoded by the paralogous genes PRKACA, PRKACB and PRKACG, respectively, and four R subunits (R1α, RIβ, RIIα and RIIβ), encoded by PKRAR1A, PKRAR1B, PKRAR2A and PKRAR2B, respectively. Yeast (Saccharomyces cerevisiae) has three C subunits (Tpk1, Tpk2, and Tpk3) encoded by the paralogous genes TPK1, TPK2 and TPK3, respectively, and a single R subunit (Bcy1) encoded by the BCY1 gene. Some validated substrates of the enzyme include cAMP-response element-binding protein (CREB), phosphorylase kinase α subunit (PHKA), and tyrosine 3-monooxygenase (TH) in mammals; Adr1, Whi3, Nej1, and Pyk1 in yeast.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 142008-29-5

References:

1.	Krebs, E.G. The Albert Lasker Medical Awards. Role of the cyclic AMP-dependent protein kinase in signal transduction. JAMA 262 (1989) 1815–1818. [DOI] [PMID: 2550680]
2.	Technikova-Dobrova, Z., Sardanelli, A.M., Speranza, F., Scacco, S., Signorile, A., Lorusso, V. and Papa, S. Cyclic adenosine monophosphate-dependent phosphorylation of mammalian mitochondrial proteins: enzyme and substrate characterization and functional role. Biochemistry 40 (2001) 13941–13947. [DOI] [PMID: 11705384]
3.	Smith, F.D., Samelson, B.K. and Scott, J.D. Discovery of cellular substrates for protein kinase A using a peptide array screening protocol. Biochem. J. 438 (2011) 103–110. [DOI] [PMID: 21644927]
4.	Broach, J.R. Nutritional control of growth and development in yeast. Genetics 192 (2012) 73–105. [DOI] [PMID: 22964838]
5.	Embogama, D.M. and Pflum, M.K. K-BILDS: a kinase substrate discovery tool. Chembiochem 18 (2017) 136–141. [DOI] [PMID: 27860220]
6.	Taylor, S.S., Wu, J., Bruystens, J.GH., Del Rio, J.C., Lu, T.W., Kornev, A.P. and Ten Eyck, L.F. From structure to the dynamic regulation of a molecular switch: A journey over 3 decades. J. Biol. Chem. 296:100746 (2021). [DOI] [PMID: 33957122]
7.	Ramms, D.J., Raimondi, F., Arang, N., Herberg, F.W., Taylor, S.S. and Gutkind, J.S. Gαs-protein kinase A (PKA) pathway signalopathies: the emerging genetic landscape and therapeutic potential of human diseases driven by aberrant Gαs-PKA signaling. Pharmacol Rev 73 (2021) 155–197. [DOI] [PMID: 34663687]

[EC 2.7.11.11 created 2005 (EC 2.7.1.37 part-incorporated 2005), modified 2022]

2.7.11.34

Accepted name:

NEK6-subfamily protein kinase

Reaction:

ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate

Other name(s):

NEK6; NEK7; nekl-3

Comments:

Requires Mg²⁺. NEK6 subfamily kinases are present in animals, though lost in insects, and include human NEK6 and NEK7 and C. elegans nekl-3. They are activated in mitosis by phosphorylation by NEK9 [1], and phosphorylate cytoskeletal proteins including EML4, KIF11A and KIF14 [4,2]. In C. elegans, nekl-3 is involved in clathrin-mediated endocytosis [5]. In peptide arrays, NEK6 prefers to phosphorylate Ser residues, with hydrophobic residues at -2 and +1 and charged residues at -1, -2 and +2 [3].

Links to other databases:

References:

1.	Belham, C., Roig, J., Caldwell, J.A., Aoyama, Y., Kemp, B.E., Comb, M. and Avruch, J. A mitotic cascade of NIMA family kinases. Nercc1/Nek9 activates the Nek6 and Nek7 kinases. J. Biol. Chem. 278 (2003) 34897–34909. [DOI] [PMID: 12840024]
2.	Cullati, S.N., Kabeche, L., Kettenbach, A.N. and Gerber, S.A. A bifurcated signaling cascade of NIMA-related kinases controls distinct kinesins in anaphase. J. Cell Biol. 216 (2017) 2339–2354. [DOI] [PMID: 28630147]
3.	van de Kooij, B., Creixell, P., van Vlimmeren, A., Joughin, B.A., Miller, C.J., Haider, N., Simpson, C.D., Linding, R., Stambolic, V., Turk, B.E. and Yaffe, M.B. Comprehensive substrate specificity profiling of the human Nek kinome reveals unexpected signaling outputs. Elife 8 (2019) . [DOI] [PMID: 31124786]
4.	Adib, R., Montgomery, J.M., Atherton, J., O'Regan, L., Richards, M.W., Straatman, K.R., Roth, D., Straube, A., Bayliss, R., Moores, C.A. and Fry, A.M. Mitotic phosphorylation by NEK6 and NEK7 reduces the microtubule affinity of EML4 to promote chromosome congression. Sci Signal 12 (2019) . [DOI] [PMID: 31409757]
5.	Joseph, B.B., Wang, Y., Edeen, P., Lazetic, V., Grant, B.D. and Fay, D.S. Control of clathrin-mediated endocytosis by NIMA family kinases. PLoS Genet. 16:e1008633 (2020). [DOI] [PMID: 32069276]

[EC 2.7.11.34 created 2022]

3.1.3.81

Transferred entry:

diacylglycerol diphosphate phosphatase. Now EC 3.6.1.75, diacylglycerol diphosphate phosphatase

[EC 3.1.3.81 created 2010, deleted 2022]

3.3.1.1

Transferred entry:

adenosylhomocysteinase, now classified as EC 3.13.2.1, adenosylhomocysteinase

[EC 3.3.1.1 created 1961, modified 2004, deleted 2022]

3.3.1.2

Transferred entry:

S-adenosyl-L-methionine hydrolase (L-homoserine-forming), now classified as EC 3.13.2.2, S-adenosyl-L-methionine hydrolase (L-homoserine-forming)

[EC 3.3.1.2 created 1972, modified 1976, modified 2018, deleted 2022]

*EC

3.4.21.109

Accepted name:

matriptase

Reaction:

Cleaves various synthetic substrates with Arg or Lys at the P1 position and prefers small side-chain amino acids, such as Ala and Gly, at the P2 position

Other name(s):

serine protease 14; membrane-type serine protease 1; MT-SP1; prostamin; serine protease TADG-15; tumor-associated differentially-expressed gene 15 protein; ST14; breast cancer 80 kDa protease; epithin; serine endopeptidase SNC19; matriptase-1; matriptase-2; matriptase-3; TMPRSS6 (gene name)

Comments:

This trypsin-like integral-membrane serine peptidase has been implicated in breast cancer invasion and metastasis [1,2]. The enzyme can activate hepatocyte growth factor/scattering factor (HGF/SF) by cleavage of the two-chain forms at an Arg residue to give active α- and β-HGF, but It does not activate plasminogen, which shares high homology with HGF [1]. The enzyme can also activate urokinase plasminogen activator (uPA), which initiates the matrix-degrading peptidase cascade [1,2]. Hemojuvelin has been shown to be a physiological substrate for matriptase-2 [5]. Belongs in peptidase family S1A.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 241475-96-7

References:

1.	Lee, S.L., Dickson, R.B. and Lin, C.Y. Activation of hepatocyte growth factor and urokinase/plasminogen activator by matriptase, an epithelial membrane serine protease. J. Biol. Chem. 275 (2000) 36720–36725. [DOI] [PMID: 10962009]
2.	Lin, C.Y., Anders, J., Johnson, M., Sang, Q.A. and Dickson, R.B. Molecular cloning of cDNA for matriptase, a matrix-degrading serine protease with trypsin-like activity. J. Biol. Chem. 274 (1999) 18231–18236. [DOI] [PMID: 10373424]
3.	Ramsay, A.J., Reid, J.C., Velasco, G., Quigley, J.P. and Hooper, J.D. The type II transmembrane serine protease matriptase-2 – identification, structural features, enzymology, expression pattern and potential roles. Front. Biosci. 13 (2008) 569–579. [DOI] [PMID: 17981570]
4.	Kojima, K., Tsuzuki, S., Fushiki, T. and Inouye, K. The activity of a type II transmembrane serine protease, matriptase, is dependent solely on the catalytic domain. Biosci. Biotechnol. Biochem. 73 (2009) 454–456. [DOI] [PMID: 19202271]
5.	Wysocka, M., Gruba, N., Miecznikowska, A., Popow-Stellmaszyk, J., Gutschow, M., Stirnberg, M., Furtmann, N., Bajorath, J., Lesner, A. and Rolka, K. Substrate specificity of human matriptase-2. Biochimie 97 (2014) 121–127. [DOI] [PMID: 24161741]

[EC 3.4.21.109 created 2006, modified 2022]

3.4.21.122

Accepted name:

transmembrane protease serine 2

Reaction:

The enzyme cleaves angiotensin-converting enzyme 2 (EC 3.4.17.23) and cleaves influenzea A and B virus and coronavirus spike glycoproteins at arginine residues.

Other name(s):

TMPRSS2 (gene name); epitheliasin

Comments:

The enzyme, present in mammalia, cleaves and inactivates EC 3.4.17.23, angiotensin-converting enzyme 2 (ACE2), at arginine residues in the region R697 to R716, which enhances influenza and coronavirus uptake [7]. The enzyme also cleaves and activates influenza and coronavirus spike glycoproteins and thus facilitates virus-cell membrane fusions. The cleavage of SARS-COV2 spike glycoprotein occurs between the S2 and S2′ site at SKPSKR/SFIEDL, while the cleavage of MERS-COV glycoprotein occurs at GSRSAR/SAIEDL.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, MEROPS, PDB

References:

1.	Jacquinet, E., Rao, N.V., Rao, G.V. and Hoidal, J.R. Cloning, genomic organization, chromosomal assignment and expression of a novel mosaic serine proteinase: epitheliasin. FEBS Lett. 468 (2000) 93–100. [DOI] [PMID: 10683448]
2.	Jacquinet, E., Rao, N.V., Rao, G.V., Zhengming, W., Albertine, K.H. and Hoidal, J.R. Cloning and characterization of the cDNA and gene for human epitheliasin. Eur. J. Biochem. 268 (2001) 2687–2699. [DOI] [PMID: 11322890]
3.	Bottcher-Friebertshauser, E., Freuer, C., Sielaff, F., Schmidt, S., Eickmann, M., Uhlendorff, J., Steinmetzer, T., Klenk, H.D. and Garten, W. Cleavage of influenza virus hemagglutinin by airway proteases TMPRSS2 and HAT differs in subcellular localization and susceptibility to protease inhibitors. J. Virol. 84 (2010) 5605–5614. [DOI] [PMID: 20237084]
4.	Bertram, S., Glowacka, I., Muller, M.A., Lavender, H., Gnirss, K., Nehlmeier, I., Niemeyer, D., He, Y., Simmons, G., Drosten, C., Soilleux, E.J., Jahn, O., Steffen, I. and Pohlmann, S. Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease. J. Virol. 85 (2011) 13363–13372. [DOI] [PMID: 21994442]
5.	Bertram, S., Dijkman, R., Habjan, M., Heurich, A., Gierer, S., Glowacka, I., Welsch, K., Winkler, M., Schneider, H., Hofmann-Winkler, H., Thiel, V. and Pohlmann, S. TMPRSS2 activates the human coronavirus 229E for cathepsin-independent host cell entry and is expressed in viral target cells in the respiratory epithelium. J. Virol. 87 (2013) 6150–6160. [DOI] [PMID: 23536651]
6.	Abe, M., Tahara, M., Sakai, K., Yamaguchi, H., Kanou, K., Shirato, K., Kawase, M., Noda, M., Kimura, H., Matsuyama, S., Fukuhara, H., Mizuta, K., Maenaka, K., Ami, Y., Esumi, M., Kato, A. and Takeda, M. TMPRSS2 is an activating protease for respiratory parainfluenza viruses. J. Virol. 87 (2013) 11930–11935. [DOI] [PMID: 23966399]
7.	Heurich, A., Hofmann-Winkler, H., Gierer, S., Liepold, T., Jahn, O. and Pohlmann, S. TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein. J. Virol. 88 (2014) 1293–1307. [DOI] [PMID: 24227843]
8.	Limburg, H., Harbig, A., Bestle, D., Stein, D.A., Moulton, H.M., Jaeger, J., Janga, H., Hardes, K., Koepke, J., Schulte, L., Koczulla, A.R., Schmeck, B., Klenk, H.D. and Bottcher-Friebertshauser, E. TMPRSS2 is the major activating protease of influenza A virus in primary human airway cells and influenza B virus in human type II pneumocytes. J. Virol. 93 (2019) . [DOI] [PMID: 31391268]
9.	Bestle, D., Heindl, M.R., Limburg, H., Van Lam van, T., Pilgram, O., Moulton, H., Stein, D.A., Hardes, K., Eickmann, M., Dolnik, O., Rohde, C., Klenk, H.D., Garten, W., Steinmetzer, T. and Bottcher-Friebertshauser, E. TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells. Life Sci Alliance 3 (2020) . [DOI] [PMID: 32703818]

[EC 3.4.21.122 created 2020]

3.6.1.75

Accepted name:

diacylglycerol diphosphate phosphatase

Reaction:

1,2-diacyl-sn-glycerol 3-diphosphate + H₂O = 1,2-diacyl-sn-glycerol 3-phosphate + phosphate

Other name(s):

DGPP phosphatase; DGPP phosphohydrolase; DPP1; DPPL1; DPPL2; PAP2; pyrophosphate phosphatase

Systematic name:

1,2-diacyl-sn-glycerol 3-phosphate phosphohydrolase

Comments:

The bifunctional enzyme catalyses the dephosphorylation of diacylglycerol diphosphate to phosphatidate and the subsequent dephosphorylation of phosphatidate to diacylglycerol (cf. phosphatidate phosphatase (EC 3.1.3.4)). It regulates intracellular levels of diacylglycerol diphosphate and phosphatidate, phospholipid molecules believed to play a signalling role in stress response [6]. The phosphatase activity of the bifunctional enzyme is Mg²⁺-independent and N-ethylmaleimide-insensitive and is distinct from the Mg²⁺-dependent and N-ethylmaleimide-sensitive enzyme EC 3.1.3.4 (phosphatidate phosphatase) [5].The diacylglycerol pyrophosphate phosphatase activity in Saccharomyces cerevisiae is induced by zinc depletion, by inositol supplementation, and when cells enter the stationary phase [4].

Links to other databases:

References:

1.	Dillon, D.A., Wu, W.I., Riedel, B., Wissing, J.B., Dowhan, W. and Carman, G.M. The Escherichia coli pgpB gene encodes for a diacylglycerol pyrophosphate phosphatase activity. J. Biol. Chem. 271 (1996) 30548–30553. [DOI] [PMID: 8940025]
2.	Dillon, D.A., Chen, X., Zeimetz, G.M., Wu, W.I., Waggoner, D.W., Dewald, J., Brindley, D.N. and Carman, G.M. Mammalian Mg²⁺-independent phosphatidate phosphatase (PAP2) displays diacylglycerol pyrophosphate phosphatase activity. J. Biol. Chem. 272 (1997) 10361–10366. [DOI] [PMID: 9099673]
3.	Wu, W.I., Liu, Y., Riedel, B., Wissing, J.B., Fischl, A.S. and Carman, G.M. Purification and characterization of diacylglycerol pyrophosphate phosphatase from Saccharomyces cerevisiae. J. Biol. Chem. 271 (1996) 1868–1876. [DOI] [PMID: 8567632]
4.	Oshiro, J., Han, G.S. and Carman, G.M. Diacylglycerol pyrophosphate phosphatase in Saccharomyces cerevisiae. Biochim. Biophys. Acta 1635 (2003) 1–9. [DOI] [PMID: 14642771]
5.	Carman, G.M. Phosphatidate phosphatases and diacylglycerol pyrophosphate phosphatases in Saccharomyces cerevisiae and Escherichia coli. Biochim. Biophys. Acta 1348 (1997) 45–55. [DOI] [PMID: 9370315]
6.	Han, G.S., Johnston, C.N., Chen, X., Athenstaedt, K., Daum, G. and Carman, G.M. Regulation of the Saccharomyces cerevisiae DPP1-encoded diacylglycerol pyrophosphate phosphatase by zinc. J. Biol. Chem. 276 (2001) 10126–10133. [DOI] [PMID: 11139591]

[EC 3.6.1.75 created 2010 as EC 3.1.3.81, 2022 transferred to EC 3.6.1.75]

3.13.1.8

Transferred entry:

S-adenosyl-L-methionine hydrolase (adenosine-forming), now classified as EC 3.13.2.3, S-adenosyl-L-methionine hydrolase (adenosine-forming)

[EC 3.13.1.8 created 2018, deleted 2022]

3.13 Acting on carbon-sulfur bonds

3.13.2 Thioether and trialkylsulfonium hydrolases

3.13.2.1

Accepted name:

adenosylhomocysteinase

Reaction:

S-adenosyl-L-homocysteine + H₂O = L-homocysteine + adenosine

For diagram of reaction mechanism, click here

Other name(s):

S-adenosylhomocysteine synthase; S-adenosylhomocysteine hydrolase (ambiguous); adenosylhomocysteine hydrolase; S-adenosylhomocysteinase; SAHase; AdoHcyase

Systematic name:

S-adenosyl-L-homocysteine hydrolase

Comments:

The enzyme contains one tightly bound NAD⁺ per subunit. This appears to bring about a transient oxidation at C-3′ of the 5′-deoxyadenosine residue, thus labilizing the thioether bond [2] (for mechanism, click here), cf. EC 5.5.1.4, inositol-3-phosphate synthase.

Links to other databases:

BRENDA, EXPASY, Gene, GTD, KEGG, PDB, CAS registry number: 9025-54-1

References:

1.	de la Haba, G. and Cantoni, G.L. The enzymatic synthesis of S-adenosyl-L-homocysteine from adenosine and homocysteine. J. Biol. Chem. 234 (1959) 603–608. [PMID: 13641268]
2.	Palmer, J.L. and Abeles, R.H. The mechanism of action of S-adenosylhomocysteinase. J. Biol. Chem. 254 (1979) 1217–1226. [PMID: 762125]

[EC 3.13.2.1 created 1961 as EC 3.3.1.1, modified 2004, transferred 2022 to EC 3.13.2.1]

3.13.2.2

Transferred entry:

S-adenosyl-L-methionine hydrolase (L-homoserine-forming). Now classified as EC 4.4.1.42, S-adenosyl-L-methionine lyase

[EC 3.13.2.2 created 1972 as EC 3.3.1.2, modified 1976, modified 2018, transferred 2022 to EC 3.13.2.2, deleted 2022]

3.13.2.3

Accepted name:

(R)-S-adenosyl-L-methionine hydrolase (adenosine-forming)

Reaction:

(R)-S-adenosyl-L-methionine + H₂O = adenosine + L-methionine

Other name(s):

SAM hydroxide adenosyltransferase

Systematic name:

(R)-S-adenosyl-L-methionine hydrolase (adenosine-forming)

Comments:

The enzyme, found in bacteria and archaea, is involved in removing the (R) isomer of S-adenosyl-L-methionine from the cell. It catalyses a nucleophilic attack of water at the C5′ carbon of S-adenosyl-L-methionine to generate adenosine and L-methionine.

Links to other databases:

References:

1.	Eustaquio, A.S., Harle, J., Noel, J.P. and Moore, B.S. S-Adenosyl-L-methionine hydrolase (adenosine-forming), a conserved bacterial and archaeal protein related to SAM-dependent halogenases. ChemBioChem 9 (2008) 2215–2219. [DOI] [PMID: 18720493]
2.	Deng, H., McMahon, S.A., Eustaquio, A.S., Moore, B.S., Naismith, J.H. and O'Hagan, D. Mechanistic insights into water activation in SAM hydroxide adenosyltransferase (duf-62). ChemBioChem 10 (2009) 2455–2459. [DOI] [PMID: 19739191]
3.	Kornfuehrer, T., Romanowski, S., de Crecy-Lagard, V., Hanson, A.D. and Eustaquio, A.S. An enzyme containing the conserved domain of unknown function DUF62 acts as a stereoselective (Rs ,Sc)-S-adenosylmethionine hydrolase. Chembiochem 21 (2020) 3495–3499. [DOI] [PMID: 32776704]

[EC 3.13.2.3 created 2018 as EC 3.13.1.8, transferred 2022 to EC 3.13.2.3]

4.1.1.122

Accepted name:

L-cysteate decarboxylase

Reaction:

L-cysteate = taurine + CO₂

Other name(s):

CAD

Systematic name:

L-cysteate carboxy-lyase (taurine-forming)

Comments:

Requires pyridoxal 5′-phosphate. The enzyme, characterized from chicken, is specific for L-cysteate and has poor activity with 3-sulfino-L-alanine. cf. EC 4.1.1.29, sulfinoalanine decarboxylase.

Links to other databases:

References:

1.	Malatesta, M., Mori, G., Acquotti, D., Campanini, B., Peracchi, A., Antin, P.B. and Percudani, R. Birth of a pathway for sulfur metabolism in early amniote evolution. Nat Ecol Evol 4 (2020) 1239–1246. [DOI] [PMID: 32601391]

[EC 4.1.1.122 created 2022]

4.1.1.123

Accepted name:

phenyl-phosphate phosphatase/carboxylase

Reaction:

4-hydroxybenzoate + phosphate = phenyl phosphate + CO₂ + H₂O

Other name(s):

phenyl phosphate carboxylase

Systematic name:

4-hydroxybenzoate carboxy-lyase (phenyl phosphate-forming)

Comments:

The enzyme, characterized from the bacterium Thauera aromatica, participates in an anaerobic phenol degradation pathway. It catalyses the para dephosphorylation and carboxylation of phenylphosphate to 4-hydroxybenzoate. The enzyme from Thauera aromatica consists of four different subunits and requires K⁺ and a divalent metal cation (Mg²⁺ or Mn²⁺) for activity. It is strongly inhibited by oxygen.

Links to other databases:

References:

1.	Schuhle, K. and Fuchs, G. Phenylphosphate carboxylase: a new C-C lyase involved in anaerobic phenol metabolism in Thauera aromatica. J. Bacteriol. 186 (2004) 4556–4567. [DOI] [PMID: 15231788]

[EC 4.1.1.123 created 2022]

*EC

4.2.1.74

Accepted name:

medium-chain-enoyl-CoA hydratase

Reaction:

a medium-chain (3S)-3-hydroxyacyl-CoA = a medium-chain trans-2-enoyl-CoA + H₂O

Glossary:

a medium-chain acyl-CoA = an acyl-CoA thioester where the acyl chain contains 6 to 12 carbon atoms.

Other name(s):

long-chain enoyl coenzyme A hydratase (incorrect); long-chain-enoyl-CoA hydratase (incorrect); long-chain-(3S)-3-hydroxyacyl-CoA hydro-lyase (incorrect)

Systematic name:

medium-chain-(3S)-3-hydroxyacyl-CoA hydro-lyase

Comments:

Acts in the reverse direction. The best substrate for the porcine enzyme is oct-2-enoyl-CoA. Unlike EC 4.2.1.17 enoyl-CoA hydratase, it does not act on crotonoyl-CoA.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 62009-81-8

References:

1.	Fong, J.C. and Schulz, H. Purification and properties of pig heart crotonase and the presence of short chain and long chain enoyl coenzyme A hydratases in pig and guinea pig tissues. J. Biol. Chem. 252 (1977) 542–547. [PMID: 833142]
2.	Schulz, H. Long chain enoyl coenzyme A hydratase from pig heart. J. Biol. Chem. 249 (1974) 2704–2709. [PMID: 4828315]
3.	Arent, S., Christensen, C.E., Pye, V.E., Norgaard, A. and Henriksen, A. The multifunctional protein in peroxisomal β-oxidation: structure and substrate specificity of the Arabidopsis thaliana protein MFP2. J. Biol. Chem. 285 (2010) 24066–24077. [DOI] [PMID: 20463021]

[EC 4.2.1.74 created 1981, modified 2022]

4.3.2.11

Accepted name:

(3R)-3-[(carboxylmethyl)amino]fatty acid synthase

Reaction:

(3R)-3-[(carboxylmethyl)amino]fatty acid + an [acyl-carrier protein] = a (2E)-unsaturated fatty acyl-[acyl-carrier protein] + glycine + H₂O

Other name(s):

scoD (gene name); mmaD (gene name)

Systematic name:

(3R)-3-[(carboxylmethyl)amino]fatty acid glycine-lyase ((2E)-unsaturated fatty acyl-[acyl-carrier protein]-forming)

Comments:

The enzyme, found in some actinobacterial species, participates in the biosynthesis of isonitrile-containing lipopeptides. It catalyses the formation of (3R)-3-[(carboxylmethyl)amino]fatty acid by the addition of glycine and the release of the product from the acyl-carrier protein.

Links to other databases:

References:

1.	Harris, N.C., Sato, M., Herman, N.A., Twigg, F., Cai, W., Liu, J., Zhu, X., Downey, J., Khalaf, R., Martin, J., Koshino, H. and Zhang, W. Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria. Proc. Natl. Acad. Sci. USA 114 (2017) 7025–7030. [DOI] [PMID: 28634299]
2.	Harris, N.C., Born, D.A., Cai, W., Huang, Y., Martin, J., Khalaf, R., Drennan, C.L. and Zhang, W. Isonitrile formation by a non-heme iron(II)-dependent oxidase/decarboxylase. Angew. Chem. Int. Ed. Engl. 57 (2018) 9707–9710. [DOI] [PMID: 29906336]

[EC 4.3.2.11 created 2022]

4.6.1.26

Accepted name:

uridylate cyclase

Reaction:

UTP = 3′,5′-cyclic UMP + diphosphate

Glossary:

3′,5′-cyclic UMP = cUMP
uridylate = CMP

Other name(s):

pycC (gene name) (ambiguous)

Systematic name:

UTP diphosphate-lyase (cyclizing; 3′,5′-cyclic-UMP-forming)

Comments:

The enzyme, found in bacteria and archaea, forms cUMP, which functions as a second messenger in bacterial immunity against viruses. The enzyme is synthesized following phage infection and activates immune effectors that execute an antiviral response.

Links to other databases:

BRENDA, EXPASY, Gene, GTD, KEGG, PDB

References:

Tal, N., Morehouse, B.R., Millman, A., Stokar-Avihail, A., Avraham, C., Fedorenko, T., Yirmiya, E., Herbst, E., Brandis, A., Mehlman, T., Oppenheimer-Shaanan, Y., Keszei, A.FA., Shao, S., Amitai, G., Kranzusch, P.J. and Sorek, R. Cyclic CMP and cyclic UMP mediate bacterial immunity against phages. Cell 184 (2021) 5728–5739.e16. [DOI] [PMID: 34644530]

[EC 4.6.1.26 created 2022]

*EC

5.3.1.31

Accepted name:

sulfoquinovose isomerase

Reaction:

(1) β-sulfoquinovose = 6-deoxy-6-sulfo-D-fructose
(2) β-sulfoquinovose = 6-sulfo-D-rhamnose

For diagram of sulphoglycolysis of sulfoquinovose, click here

Glossary:

sulfoquinovose = 6-deoxy-6-sulfo-D-glucopyranose

Other name(s):

yihS (gene name)

Systematic name:

6-deoxy-6-sulfo-β-D-glucopyranose aldose-ketose-isomerase

Comments:

The enzyme, characterized from the bacterium Escherichia coli, is involved in the degradation pathway of sulfoquinovose, the polar headgroup of sulfolipids found in the photosynthetic membranes of all higher plants, mosses, ferns, algae, and most photosynthetic bacteria, as well as the surface layer of some archaea.

Links to other databases:

References:

1.	Denger, K., Weiss, M., Felux, A.K., Schneider, A., Mayer, C., Spiteller, D., Huhn, T., Cook, A.M. and Schleheck, D. Sulphoglycolysis in Escherichia coli K-12 closes a gap in the biogeochemical sulphur cycle. Nature 507 (2014) 114–117. [DOI] [PMID: 24463506]
2.	Sharma, M., Abayakoon, P., Epa, R., Jin, Y., Lingford, J.P., Shimada, T., Nakano, M., Mui, J.W., Ishihama, A., Goddard-Borger, E.D., Davies, G.J. and Williams, S.J. Molecular basis of sulfosugar selectivity in sulfoglycolysis. ACS Cent. Sci. 7 (2021) 476–487. [DOI] [PMID: 33791429]

[EC 5.3.1.31 created 2014, modified 2022]

5.3.1.37

Accepted name:

4-deoxy-4-sulfo-D-erythrose isomerase

Reaction:

4-deoxy-4-sulfo-D-erythrose = 4-deoxy-4-sulfo-D-erythrulose

Other name(s):

sqwI (gene name)

Systematic name:

4-deoxy-4-sulfo-D-erythrose ketose-aldose isomerase

Comments:

The enzyme, characterized from the bacterium Clostridium sp. MSTE9, is involved in a D-sulfoquinovose degradation pathway.

Links to other databases:

References:

1.	Liu, J., Wei, Y., Ma, K., An, J., Liu, X., Liu, Y., Ang, E.L., Zhao, H. and Zhang, Y. Mechanistically diverse pathways for sulfoquinovose degradation in bacteria. ACS Catal. 11 (2021) 14740–14750. [DOI]

[EC 5.3.1.37 created 2022]

6.2.1.76

Accepted name:

malonate—CoA ligase

Reaction:

ATP + malonate + CoA = AMP + diphosphate + malonyl-CoA

Other name(s):

ACSF3 (gene name); AAE13 (gene name); malonyl-CoA synthetase

Systematic name:

malonate:CoA ligase (AMP-forming)

Comments:

The enzyme, found in mitochondria, detoxifies malonate, which is a potent inhibitor of mitochondrial respiration, and provides malonyl-CoA to the mitochondrial fatty acid biosynthesis pathway.

Links to other databases:

References:

1.	Gueguen, V., Macherel, D., Jaquinod, M., Douce, R. and Bourguignon, J. Fatty acid and lipoic acid biosynthesis in higher plant mitochondria. J. Biol. Chem. 275 (2000) 5016–5025. [DOI] [PMID: 10671542]
2.	Witkowski, A., Thweatt, J. and Smith, S. Mammalian ACSF3 protein is a malonyl-CoA synthetase that supplies the chain extender units for mitochondrial fatty acid synthesis. J. Biol. Chem. 286 (2011) 33729–33736. [DOI] [PMID: 21846720]
3.	Chen, H., Kim, H.U., Weng, H. and Browse, J. Malonyl-CoA synthetase, encoded by Acyl Activating Enzyme13, is essential for growth and development of Arabidopsis. Plant Cell 23 (2011) 2247–2262. [DOI] [PMID: 21642549]
4.	Guan, X. and Nikolau, B.J. AAE13 encodes a dual-localized malonyl-CoA synthetase that is crucial for mitochondrial fatty acid biosynthesis. Plant J. 85 (2016) 581–593. [DOI] [PMID: 26836315]
5.	Bowman, C.E., Rodriguez, S., Selen Alpergin, E.S., Acoba, M.G., Zhao, L., Hartung, T., Claypool, S.M., Watkins, P.A. and Wolfgang, M.J. The mammalian malonyl-CoA synthetase ACSF3 is required for mitochondrial protein malonylation and metabolic efficiency. Cell Chem. Biol. 24 (2017) 673–684.e4. [DOI] [PMID: 28479296]
6.	Bowman, C.E. and Wolfgang, M.J. Role of the malonyl-CoA synthetase ACSF3 in mitochondrial metabolism. Adv Biol Regul 71 (2019) 34–40. [DOI] [PMID: 30201289]

[EC 6.2.1.76 created 2022]

7.1.1.12

Accepted name:

succinate dehydrogenase (electrogenic, proton-motive force generating)

Reaction:

succinate + menaquinone + 2 H⁺_{[side 1]} = fumarate + menaquinol + 2 H⁺_{[side 2]}

Systematic name:

succinate:quinone oxidoreductase (electrogenic, proton-motive force generating)

Comments:

The enzyme is very similar to EC 1.3.5.1, succinate dehydrogenase, but differs by containing two heme molecules (located in the membrane anchor component) in addition to FAD and three iron-sulfur clusters. Unlike EC 1.3.5.1, this enzyme catalyses an electrogenic reaction, enabled by electron-bifurcation via the heme molecules. In the direction of succinate oxidation by menaquinone, which is endergonic, the reaction is driven by the transmembrane electrochemical proton potential. In the direction of fumarate reduction, the electrogenic electron transfer reaction is compensated by transmembrane proton transfer pathway known as the E-pathway, which results in overall electroneutrality.

Links to other databases: