Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB)

Proposed Changes to the Enzyme List

The entries below are proposed additions and amendments to the Enzyme Nomenclature list. The entries below are proposed additions and amendments to the Enzyme Nomenclature list. They were prepared for the NC-IUBMB by Kristian Axelsen, Ron Caspi, Masaaki Kotera, Andrew McDonald, Gerry Moss, Dietmar Schomburg, Ida Schomburg and Keith Tipton. Comments and suggestions on these draft entries should be sent to Dr Andrew McDonald (Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland). The date on which an enzyme will be made official is appended after the EC number. To prevent confusion please do not quote new EC numbers until they are incorporated into the main list.

An asterisk before "EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.


Contents

*EC 1.1.1.21 aldose reductase (1 January 2020)
EC 1.1.1.420 D-apiose dehydrogenase (1 January 2020)
EC 1.1.1.421 D-apionate oxidoisomerase (1 January 2020)
EC 1.1.2.10 lanthanide-dependent methanol dehydrogenase (1 January 2020)
*EC 1.2.1.25 branched-chain α-keto acid dehydrogenase system (1 January 2020)
EC 1.2.1.103 [amino group carrier protein]-6-phospho-L-2-aminoadipate reductase (1 January 2020)
EC 1.3.1.99 deleted, now known to be catalyzed by EC 1.3.1.122 and EC 5.5.1.34 (1 January 2020)
EC 1.3.1.121 4-amino-4-deoxyprephenate dehydrogenase (1 January 2020)
EC 1.3.1.122 (S)-8-oxocitronellyl enol synthase (1 January 2020)
EC 1.3.1.123 7-epi-iridoid synthase (1 January 2020)
EC 1.3.8.15 3-(aryl)acrylate reductase (1 January 2020)
*EC 1.6.5.9 NADH:quinone reductase (non-electrogenic) (1 January 2020)
EC 1.6.5.11 deleted, identical to EC 1.6.5.9 (1 January 2020)
EC 1.8.4.15 protein dithiol oxidoreductase (disulfide-forming) (1 January 2020)
EC 1.8.4.16 thioredoxin:protein disulfide reductase (1 January 2020)
EC 1.8.5.9 protein dithiol:quinone oxidoreductase DsbB (1 January 2020)
EC 1.9.3.1transferred, now EC 7.1.1.9 (1 January 2020)
EC 1.10.3.17 superoxide oxidase (1 January 2020)
*EC 1.13.11.79 aerobic 5,6-dimethylbenzimidazole synthase (1 January 2020)
EC 1.14.11.70 7-deoxycylindrospermopsin hydroxylase (1 January 2020)
EC 1.14.11.71 methylphosphonate hydroxylase (1 January 2020)
EC 1.14.13.247 stachydrine N-demethylase (1 January 2020)
*EC 1.14.14.22 dibenzothiophene sulfone monooxygenase (1 January 2020)
*EC 1.14.16.1 phenylalanine 4-monooxygenase (1 January 2020)
*EC 1.14.16.2 tyrosine 3-monooxygenase (1 January 2020)
*EC 1.14.16.4 tryptophan 5-monooxygenase (1 January 2020)
*EC 1.14.16.7 phenylalanine 3-monooxygenase (1 January 2020)
*EC 1.14.17.3 peptidylglycine monooxygenase (1 January 2020)
*EC 1.14.99.46 pyrimidine oxygenase (1 January 2020)
EC 1.16.8.1 deleted, now known to be catalysed by EC 2.5.1.17 (1 January 2020)
*EC 2.1.1.74 methylenetetrahydrofolate—tRNA-(uracil54-C5)-methyltransferase [NAD(P)H-oxidizing] (1 January 2020)
EC 2.1.1.363 pre-sodorifen synthase (1 January 2020)
*EC 2.3.1.291 sphingoid base N-palmitoyltransferase (1 January 2020)
EC 2.3.2.33 RCR-type E3 ubiquitin transferase (1 January 2020)
EC 2.4.1.371 polymannosyl GlcNAc-diphospho-ditrans,octacis-undecaprenol 2,3-α-mannosylpolymerase (1 January 2020)
EC 2.4.1.372 mutansucrase (1 January 2020)
EC 2.4.1.373 α-(1→2) branching sucrase (1 January 2020)
EC 2.4.1.374 β-1,2-mannooligosaccharide synthase (1 January 2020)
EC 2.6.1.118 [amino group carrier protein]-γ-(L-lysyl)-L-glutamate aminotransferase (1 January 2020)
EC 2.7.1.230 amicoumacin kinase (1 January 2020)
EC 2.7.2.16 2-phosphoglycerate kinase (1 January 2020)
EC 3.1.3.107 amicoumacin phosphatase (1 January 2020)
EC 3.1.11.7 transferred, now EC 3.6.1.71 (1 January 2020)
EC 3.1.11.8 transferred, now EC 3.6.1.70 (1 January 2020)
EC 3.1.12.2 transferred, now EC 3.6.1.72 (1 January 2020)
EC 3.6.1.69 8-oxo-(d)GTP phosphatase (1 January 2020)
EC 3.6.1.70 guanosine-5'-diphospho-5'-[DNA] diphosphatase (1 January 2020)
EC 3.6.1.71 adenosine-5'-diphospho-5'-[DNA] diphosphatase (1 January 2020)
EC 3.6.1.72 DNA-3'-diphospho-5'-guanosine diphosphatase (1 January 2020)
EC 4.1.1.119 phenylacetate decarboxylase (1 January 2020)
*EC 4.3.2.5 peptidylamidoglycolate lyase (1 January 2020)
EC 5.5.1.34 (+)-cis,trans-nepetalactol synthase (1 January 2020)
EC 5.5.1.35 (+)-cis,cis-nepetalactol synthase (1 January 2020)
EC 6.2.1.61 salicylate—[aryl-carrier protein] ligase (1 January 2020)
*EC 6.3.2.43 [amino group carrier protein]—L-2-aminoadipate ligase (1 January 2020)
*EC 6.3.2.52 jasmonoyl—L-amino acid ligase (1 January 2020)
EC 7.1.1.9 cytochrome-c oxidase (1 January 2020)
EC 7.4.2.13 ABC-type tyrosine transporter (1 January 2020)

*EC 1.1.1.21

Accepted name: aldose reductase

Reaction: alditol + NAD(P)+ = aldose + NAD(P)H + H+

Other name(s): polyol dehydrogenase (NADP+); ALR2; alditol:NADP+ oxidoreductase; alditol:NADP+ 1-oxidoreductase; NADPH-aldopentose reductase; NADPH-aldose reductase; aldehyde reductase (misleading)

Systematic name: alditol:NAD(P)+ 1-oxidoreductase

Comments: Has wide specificity.

Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9028-31-3

References:

1. Attwood, M.A. and Doughty, C.C. Purification and properties of calf liver aldose reductase. Biochim. Biophys. Acta 370 (1974) 358-368. [PMID: 4216364]

2. Boghosian, R.A. and McGuinness, E.T. Affinity purification and properties of porcine brain aldose reductase. Biochim. Biophys. Acta 567 (1979) 278-286. [PMID: 36151]

3. Hers, H.G. L’Aldose-réductase. Biochim. Biophys. Acta 37 (1960) 120-126. [PMID: 14401390]

4. Scher, B.M. and Horecker, B.L. Pentose metabolism in Candida. 3. The triphosphopyridine nucleotide-specific polyol dehydrogenase of Candida utilis. Arch. Biochem. Biophys. 116 (1966) 117-128. [PMID: 4381350]

[EC 1.1.1.21 created 1961 (EC 1.1.1.139 created 1972, incorporated 1978), modified 2019]

EC 1.1.1.420

Accepted name: D-apiose dehydrogenase

Reaction: D-apiofuranose + NAD+ = D-apionolactone + NADH + H+

Other name(s): apsD (gene name)

Systematic name: D-apiofuranose:NAD+ 1-oxidoreductase

Comments: The enzyme, characterized from several bacterial species, is involved in a catabolic pathway for D-apiose.

References:

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

[EC 1.1.1.420 created 2019]

EC 1.1.1.421

Accepted name: D-apionate oxidoisomerase

Reaction: D-apionate + NAD+ = 3-oxo-D-isoapionate + NADH + H+

Glossary: 3-oxo-D-isoapionate = 2,4-dihydroxy-2-(hydroxymethyl)-3-oxobutanoate

Other name(s): apnO (gene name)

Systematic name: D-apionate:NAD+ oxidoreductase (isomerizing)

Comments: The enzyme, characterized from several bacterial species, participates in the degradation of D-apionate. The reaction involves migration of a hydroxymethyl group from position 3 to position 2 and oxidation of the 3-hydroxyl group.

References:

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

[EC 1.1.1.421 created 2019]

EC 1.1.2.10

Accepted name: lanthanide-dependent methanol dehydrogenase

Reaction: methanol + 2 oxidized cytochrome cL = formaldehyde + 2 reduced cytochrome cL

Other name(s): XoxF; XoxF-MDH; Ce-MDH; La3+-dependent MDH; Ce3+-induced methanol dehydrogenase; cerium dependent MDH

Systematic name: methanol:cytochrome cL oxidoreductase

Comments: Isolated from the bacterium Methylacidiphilum fumariolicum and many Methylobacterium species. Requires La3+, Ce3+, Pr3+ or Nd3+. The higher lanthanides show decreasing activity with Sm3+, Eu3+ and Gd3+. The lanthanide is coordinated by the enzyme and pyrroloquinoline quinone. Shows little activity with Ca2+, the required cofactor of EC 1.1.2.7, methanol dehydrogenase (cytochrome c).

References:

1. Hibi, Y., Asai, K., Arafuka, H., Hamajima, M., Iwama, T. and Kawai, K. Molecular structure of La3+-induced methanol dehydrogenase-like protein in Methylobacterium radiotolerans. J. Biosci. Bioeng. 111 (2011) 547-549. [PMID: 21256798]

2. Nakagawa, T., Mitsui, R., Tani, A., Sasa, K., Tashiro, S., Iwama, T., Hayakawa, T. and Kawai, K. A catalytic role of XoxF1 as La3+-dependent methanol dehydrogenase in Methylobacterium extorquens strain AM1. PLoS One 7 (2012) e50480. [PMID: 23209751]

3. Pol, A., Barends, T.R., Dietl, A., Khadem, A.F., Eygensteyn, J., Jetten, M.S. and Op den Camp, H.J. Rare earth metals are essential for methanotrophic life in volcanic mudpots. Environ Microbiol 16 (2014) 255-264. [PMID: 24034209]

4. Bogart, J.A., Lewis, A.J. and Schelter, E.J. DFT study of the active site of the XoxF-type natural, cerium-dependent methanol dehydrogenase enzyme. Chemistry Eur. J. 21 (2015) 1743-1748. [PMID: 25421364]

5. Prejano, M., Marino, T. and Russo, N. How can methanol dehydrogenase from Methylacidiphilum fumariolicum work with the alien Ce(III) ion in the active center? A theoretical study. Chemistry 23 (2017) 8652-8657. [PMID: 28488399]

6. Masuda, S., Suzuki, Y., Fujitani, Y., Mitsui, R., Nakagawa, T., Shintani, M. and Tani, A. Lanthanide-dependent regulation of methylotrophy in Methylobacterium aquaticum strain 22A. mSphere 3 (2018) e00462. [PMID: 29404411]

[EC 1.1.2.10 created 2019]

*EC 1.2.1.25

Accepted name: branched-chain α-keto acid dehydrogenase system

Reaction: 3-methyl-2-oxobutanoate + CoA + NAD+ = 2-methylpropanoyl-CoA + CO2 + NADH

Other name(s): branched-chain α-keto acid dehydrogenase complex; 2-oxoisovalerate dehydrogenase; α-ketoisovalerate dehydrogenase; 2-oxoisovalerate dehydrogenase (acylating)

Systematic name: 3-methyl-2-oxobutanoate:NAD+ 2-oxidoreductase (CoA-methyl-propanoylating)

Comments: This enzyme system catalyses the oxidative decarboxylation of branched-chain α-keto acids derived from L-leucine, L-isoleucine, and L-valine to branched-chain acyl-CoAs. It belongs to the 2-oxo acid dehydrogenase system family, which also includes the pyruvate dehydrogenase system, 2-oxoglutarate dehydrogenase system, and glycine cleavage system. With the exception of the glycine cleavage system, the 2-oxo acid dehydrogenase systems share a common structure, consisting of three main components, namely a 2-oxo acid dehydrogenase (E1), a dihydrolipoamide acyltransferase (E2), and dihydrolipoamide dehydrogenase (E3). The reaction catalysed by this system is the sum of three activities: EC 1.2.4.4, 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring), EC 2.3.1.168, dihydrolipoyllysine-residue (2-methylpropanoyl)transferase, and EC 1.8.1.4, dihydrolipoyl dehydrogenase. The system also acts on (S)-3-methyl-2-oxopentanoate and 4-methyl-2-oxopentanoate.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37211-61-3

References:

1. Namba, Y., Yoshizawa, K., Ejima, A., Hayashi, T. and Kaneda, T. Coenzyme A- and nicotinamide adenine dinucleotide-dependent branched chain α-keto acid dehydrogenase. I. Purification and properties of the enzyme from Bacillus subtilis. J. Biol. Chem. 244 (1969) 4437-4447. [PMID: 4308861]

2. Pettit, F.H., Yeaman, S.J. and Reed, L.J. Purification and characterization of branched chain α-keto acid dehydrogenase complex of bovine kidney. Proc. Natl. Acad. Sci. USA, 75 (1978) 4881-4885. [PMID: 283398]

3. Harris, R.A., Hawes, J.W., Popov, K.M., Zhao, Y., Shimomura, Y., Sato, J., Jaskiewicz, J. and Hurley, T.D. Studies on the regulation of the mitochondrial α-ketoacid dehydrogenase complexes and their kinases. Adv. Enzyme Regul. 37 (1997) 271-293. [PMID: 9381974]

4. Evarsson, A., Chuang, J.L., Wynn, R.M., Turley, S., Chuang, D.T. and Hol, W.G. Crystal structure of human branched-chain α-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease. Structure 8 (2000) 277-291. [PMID: 10745006]

5. Reed, L.J. A trail of research from lipoic acid to α-keto acid dehydrogenase complexes. J. Biol. Chem 276 (2001) 38329-38336. [PMID: 11477096]

[EC 1.2.1.25 created 1972, modified 2019]

EC 1.2.1.103

Accepted name: [amino group carrier protein]-6-phospho-L-2-aminoadipate reductase

Reaction: an [amino group carrier protein]-C-terminal-N-(1-carboxy-5-oxopentan-1-yl)-L-glutamine + phosphate + NADP+ = an [amino group carrier protein]-C-terminal-N-(1-carboxy-5-phosphooxy-5-oxopentan-1-yl)-L-glutamine + NADPH + H+

Other name(s): lysY (gene name)

Systematic name: [amino group carrier protein]-C-terminal-N-(1-carboxy-5-oxopentan-1-yl)-L-glutamine:NADP+ 5-oxidoreductase (phosphorylating)

Comments: The enzyme participates in an L-lysine biosynthesis in certain species of archaea and bacteria.

References:

1. Nishida, H., Nishiyama, M., Kobashi, N., Kosuge, T., Hoshino, T. and Yamane, H. A prokaryotic gene cluster involved in synthesis of lysine through the amino adipate pathway: a key to the evolution of amino acid biosynthesis. Genome Res 9 (1999) 1175-1183. [PMID: 10613839]

2. Horie, A., Tomita, T., Saiki, A., Kono, H., Taka, H., Mineki, R., Fujimura, T., Nishiyama, C., Kuzuyama, T. and Nishiyama, M. Discovery of proteinaceous N-modification in lysine biosynthesis of Thermus thermophilus. Nat. Chem. Biol. 5 (2009) 673-679. [PMID: 19620981]

3. Shimizu, T., Tomita, T., Kuzuyama, T. and Nishiyama, M. Crystal Structure of the LysY.LysW Complex from Thermus thermophilus. J. Biol. Chem 291 (2016) 9948-9959. [PMID: 26966182]

[EC 1.2.1.103 created 2019]

[EC 1.3.1.99 Deleted entry: iridoid synthase. Now known to be catalyzed by two different enzymes, EC 1.3.1.122, (S)-8-oxocitronellyl enol synthase, and EC 5.5.1.34, (+)-cis,trans-nepetalactol synthase (EC 1.3.1.99 created 2013, deleted 2019)]

EC 1.3.1.121

Accepted name: 4-amino-4-deoxyprephenate dehydrogenase

Reaction: 4-amino-4-deoxyprephenate + NAD+ = 3-(4-aminophenyl)pyruvate + CO2 + NADH + H+

Other name(s): cmlC (gene name); papC (gene name)

Systematic name: 4-amino-4-deoxyprephenate:NAD+ oxidoreductase (decarboxylating)

Comments: The enzyme, characterized from the bacteria Streptomyces venezuelae and Streptomyces pristinaespiralis, participates in the biosynthesis of the antibiotics chloramphenicol and pristinamycin IA, respectively. cf. EC 1.3.1.12, prephenate dehydrogenase.

References:

1. Blanc, V., Gil, P., Bamas-Jacques, N., Lorenzon, S., Zagorec, M., Schleuniger, J., Bisch, D., Blanche, F., Debussche, L., Crouzet, J. and Thibaut, D. Identification and analysis of genes from Streptomyces pristinaespiralis encoding enzymes involved in the biosynthesis of the 4-dimethylamino-L-phenylalanine precursor of pristinamycin I. Mol. Microbiol. 23 (1997) 191-202. [PMID: 9044253]

2. He, J., Magarvey, N., Piraee, M. and Vining, L.C. The gene cluster for chloramphenicol biosynthesis in Streptomyces venezuelae ISP5230 includes novel shikimate pathway homologues and a monomodular non-ribosomal peptide synthetase gene. Microbiology 147 (2001) 2817-2829. [PMID: 11577160]

[EC 1.3.1.121 created 2019]

EC 1.3.1.122

Accepted name: (S)-8-oxocitronellyl enol synthase

Reaction: (S)-8-oxocitronellyl enol + NAD(P)+ = (6E)-8-oxogeranial + NAD(P)H + H+

For diagram of reactionclick here

Glossary: (S)-8-oxocitronellyl enol = (2E,6S,7E)-8-hydroxy-2,6-dimethylocta-2,7-dienal

Other name(s): CrISY; 8-oxogeranial:NAD(P)+ oxidoreductase (cyclizing, cis,trans-nepetalactol forming); iridoid synthase (incorrect)

Systematic name: (S)-8-oxocitronellyl enol:NAD(P)+ oxidoreductase

Comments: Isolated from the plants Catharanthus roseus, Olea europaea (common olive), and several Nepeta species. The enzyme reduces 8-oxogeranial, generating an unstable product that is subsequently cyclized into several possible products, either non-enzymically or by dedicated cyclases. The products, known as iridoids, are involved in the biosynthesis of many indole alkaloids. cf. EC 1.3.1.123, 7-epi-iridoid synthase.

References:

1. Geu-Flores, F., Sherden, N.H., Courdavault, V., Burlat, V., Glenn, W.S., Wu, C., Nims, E., Cui, Y. and O'Connor, S.E. An alternative route to cyclic terpenes by reductive cyclization in iridoid biosynthesis. Nature 492 (2012) 138-142. [PMID: 23172143]

2. Hu, Y., Liu, W., Malwal, S.R., Zheng, Y., Feng, X., Ko, T.P., Chen, C.C., Xu, Z., Liu, M., Han, X., Gao, J., Oldfield, E. and Guo, R.T. Structures of iridoid synthase from Catharanthus roseus with bound NAD(+) , NADPH, or NAD(+) /10-oxogeranial: Reaction mechanisms. Angew. Chem. Int. Ed. Engl. 54 (2015) 15478-15482. [PMID: 26768532]

3. Alagna, F., Geu-Flores, F., Kries, H., Panara, F., Baldoni, L., O'Connor, S.E. and Osbourn, A. Identification and characterization of the iridoid synthase involved in oleuropein biosynthesis in olive (Olea europaea) fruits. J. Biol. Chem 291 (2016) 5542-5554. [PMID: 26709230]

4. Qin, L., Zhu, Y., Ding, Z., Zhang, X., Ye, S. and Zhang, R. Structure of iridoid synthase in complex with NADP(+)/8-oxogeranial reveals the structural basis of its substrate specificity. J. Struct. Biol. 194 (2016) 224-230. [PMID: 26868105]

5. Sherden, N.H., Lichman, B., Caputi, L., Zhao, D., Kamileen, M.O., Buell, C.R. and O'Connor, S.E. Identification of iridoid synthases from Nepeta species: Iridoid cyclization does not determine nepetalactone stereochemistry. Phytochemistry 145 (2018) 48-56. [PMID: 29091815]

6. Lichman, B.R., Kamileen, M.O., Titchiner, G.R., Saalbach, G., Stevenson, C.EM., Lawson, D.M. and O'Connor, S.E. Uncoupled activation and cyclization in catmint reductive terpenoid biosynthesis. Nat. Chem. Biol. 15 (2019) 71-79. [PMID: 30531909]

7. Lichman, B.R., O'Connor, S.E. and Kries, H. Biocatalytic strategies towards [4+2] cycloadditions. Chemistry 25 (2019) 6864-6877. [PMID: 30664302]

[EC 1.3.1.122 created 2013 as EC 1.3.1.99, part transferred 2019 to EC 1.3.1.122]

EC 1.3.1.123

Accepted name: 7-epi-iridoid synthase

Reaction: (R)-8-oxocitronellyl enol + NADP+ = (6E)-8-oxogeranial + NADPH + H+

Glossary: (R)-8-oxocitronellyl enol = (2E,6R,7E)-8-hydroxy-2,6-dimethylocta-2,7-dienal

Other name(s): AmISY

Systematic name: (R)-8-oxocitronellyl enol:NADP+ oxidoreductase

Comments: The enzyme, characterized from the plant Antirrhinum majus (snapdragon), is involved in biosynthesis of 7-epi-iridoids such as antirrhinoside. The enzyme catalyses the stereospecific reduction of 8-oxogeranial, forming an unstable product that in the absence of additional cylases undergoes spontaneous cyclization to (–)-cis,trans-nepetalactol. cf. EC 1.3.1.122, (S)-8-oxocitronellyl enol synthase.

References:

1. Kries, H., Kellner, F., Kamileen, M.O. and O'Connor, S.E. Inverted stereocontrol of iridoid synthase in snapdragon. J. Biol. Chem 292 (2017) 14659-14667. [PMID: 28701463]

2. Lichman, B.R., O'Connor, S.E. and Kries, H. Biocatalytic strategies towards [4+2] cycloadditions. Chemistry 25 (2019) 6864-6877. [PMID: 30664302]

[EC 1.3.1.123 created 2019]

EC 1.3.8.15

Accepted name: 3-(aryl)acrylate reductase

Reaction: (1) phloretate + electron-transfer flavoprotein = 4-coumarate + reduced electron-transfer flavoprotein
(2) 3-phenylpropanoate + electron-transfer flavoprotein = trans-cinnamate + reduced electron-transfer flavoprotein
(3) 3-(1H-indol-3-yl)propanoate + electron-transfer flavoprotein = 3-(indol-3-yl)acrylate + reduced electron-transfer flavoprotein

Glossary: phloretate = 3-(4-hydroxyphenyl)propanoate
crotonate = (2E)-but-2-enoate

Other name(s): acdA (gene name)

Systematic name: 3-(phenyl)propanoate:electron-transfer flavoprotein 2,3-oxidoreductase

Comments: The enzyme, found in some amino acid-fermenting anaerobic bacteria, participates in the fermentation pathways of L-phenylalanine, L-tyrosine, and L-tryptophan. Unlike EC 1.3.1.31, 2-enoate reductase, this enzyme has minimal activity with crotonate.

References:

1. Dodd, D., Spitzer, M.H., Van Treuren, W., Merrill, B.D., Hryckowian, A.J., Higginbottom, S.K., Le, A., Cowan, T.M., Nolan, G.P., Fischbach, M.A. and Sonnenburg, J.L. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature 551 (2017) 648-652. [PMID: 29168502]

[EC 1.3.8.15 created 2019]

*EC 1.6.5.9

Accepted name: NADH:quinone reductase (non-electrogenic)

Reaction: NADH + H+ + a quinone = NAD+ + a quinol

Other name(s): type II NAD(P)H:quinone oxidoreductase; NDE2 (gene name); ndh (gene name); NDH-II; NDH-2; NADH dehydrogenase (quinone) (ambiguous); ubiquinone reductase (ambiguous); coenzyme Q reductase (ambiguous); dihydronicotinamide adenine dinucleotide-coenzyme Q reductase (ambiguous); DPNH-coenzyme Q reductase (ambiguous); DPNH-ubiquinone reductase (ambiguous); NADH-coenzyme Q oxidoreductase (ambiguous); NADH-coenzyme Q reductase (ambiguous); NADH-CoQ oxidoreductase (ambiguous); NADH-CoQ reductase (ambiguous); NADH-ubiquinone reductase (ambiguous); NADH-ubiquinone oxidoreductase (ambiguous); reduced nicotinamide adenine dinucleotide-coenzyme Q reductase (ambiguous); NADH-Q6 oxidoreductase (ambiguous); NADH2 dehydrogenase (ubiquinone) (ambiguous); NADH:ubiquinone oxidoreductase; NADH:ubiquinone reductase (non-electrogenic)

Systematic name: NADH:quinone oxidoreductase

Comments: A flavoprotein (FAD or FMN). Occurs in mitochondria of yeast and plants, and in aerobic bacteria. Has low activity with NADPH. Unlike EC 7.1.1.2, NADH:ubiquinone reductase (H+-translocating), this enzyme does not pump proteons of sodium ions across the membrane. It is also not sensitive to rotenone.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9028-04-0

References:

1. Bergsma, J., Strijker, R., Alkema, J.Y., Seijen, H.G. and Konings, W.N. NADH dehydrogenase and NADH oxidation in membrane vesicle from Bacillus subtilis. Eur. J. Biochem. 120 (1981) 599-606. [PMID: 6800784]

2. Møller, I.M, and Palmer, J.M. Direct evidence for the presence of a rotenone-resistant NADH dehydrogenase on the inner surface of plant mitochondria. Physiol. Plant. 54 (1982) 267-274.

3. de Vries, S. and Grivell, L.A. Purification and characterization of a rotenone-insensitive NADH:Q6 oxidoreductase from mitochondria of Saccharomyces cerevisiae. Eur. J. Biochem. 176 (1988) 377-384. [PMID: 3138118]

4. Kerscher, S.J., Okun, J.G. and Brandt, U. A single external enzyme confers alternative NADH:ubiquinone oxidoreductase activity in Yarrowia lipolytica. J. Cell Sci. 112 ( Pt 14) (1999) 2347-2354. [PMID: 10381390]

5. Rasmusson, A.G., Soole, K.L. and Elthon, T.E. Alternative NAD(P)H dehydrogenases of plant mitochondria. Annu. Rev. Plant Biol. 55 (2004) 23-39. [PMID: 15725055]

6. Melo, A.M., Bandeiras, T.M. and Teixeira, M. New insights into type II NAD(P)H:quinone oxidoreductases. Microbiol. Mol. Biol. Rev. 68 (2004) 603-616. [PMID: 15590775]

[EC 1.6.5.9 created 2011 (EC 1.6.5.11 created 1972 as EC 1.6.99.5, transferred 2015 to EC 1.6.5.11, incorporated 2019), modified 2019]

[EC 1.6.5.11 Deleted entry: NADH dehydrogenase (quinone). Identical to EC 1.6.5.9, NADH:quinone reductase (non-electrogenic) (EC 1.6.5.11 created 1972 as EC 1.6.99.5, transferred 2015 to EC 1.6.5.11, deleted 2019)]

EC 1.8.4.15

Accepted name: protein dithiol oxidoreductase (disulfide-forming)

Reaction: a [DsbA protein] carrying a disulfide bond + a [protein] with reduced L-cysteine residues = a [DsbA protein] with reduced L-cysteine residues + a [protein] carrying a disulfide bond

Other name(s): dsbA (gene name)

Systematic name: protein dithiol:[DsbA protein] oxidoreductase (protein disulfide-forming)

Comments: DsbA is a periplasmic thiol:disulfide oxidoreductase found in Gram-negative bacteria that promotes protein disulfide bond formation. DsbA contains a redox active disulfide bond that is catalytically transferred via disulfide exchange to a diverse range of newly translocated protein substrates. The protein is restored to the oxidized state by EC 1.8.5.9, protein dithiol:quinone oxidoreductase DsbB.

References:

1. Bardwell, J.C., McGovern, K. and Beckwith, J. Identification of a protein required for disulfide bond formation in vivo. Cell 67 (1991) 581-589. [PMID: 1934062]

2. Akiyama, Y., Kamitani, S., Kusukawa, N. and Ito, K. In vitro catalysis of oxidative folding of disulfide-bonded proteins by the Escherichia coli dsbA (ppfA) gene product. J. Biol. Chem 267 (1992) 22440-22445. [PMID: 1429594]

3. Zapun, A., Bardwell, J.C. and Creighton, T.E. The reactive and destabilizing disulfide bond of DsbA, a protein required for protein disulfide bond formation in vivo. Biochemistry 32 (1993) 5083-5092. [PMID: 8494885]

4. Bader, M., Muse, W., Zander, T. and Bardwell, J. Reconstitution of a protein disulfide catalytic system. J. Biol. Chem 273 (1998) 10302-10307. [PMID: 9553083]

5. Guddat, L.W., Bardwell, J.C. and Martin, J.L. Crystal structures of reduced and oxidized DsbA: investigation of domain motion and thiolate stabilization. Structure 6 (1998) 757-767. [PMID: 9655827]

6. Kadokura, H., Tian, H., Zander, T., Bardwell, J.C. and Beckwith, J. Snapshots of DsbA in action: detection of proteins in the process of oxidative folding. Science 303 (2004) 534-537. [PMID: 14739460]

[EC 1.8.4.15 created 2019]

EC 1.8.4.16

Accepted name: thioredoxin:protein disulfide reductase

Reaction: a [protein] with reduced L-cysteine residues + thioredoxin disulfide = a [protein] carrying a disulfide bond + thioredoxin (overall reaction)
(1a) a [DsbD protein] with reduced L-cysteine residues + thioredoxin disulfide = a [DsbD protein] carrying a disulfide bond + thioredoxin
(1b) a [DsbD protein] carrying a disulfide bond + a [protein] with reduced L-cysteine residues = a [DsbD protein] with reduced L-cysteine residues + a [protein] carrying a disulfide bond

Other name(s): dsbD (gene name); dipZ (gene name)

Systematic name: thioredoxin:protein disulfide oxidoreductase (dithiol-forming)

Comments: DsbD is an inner membrane protein found in Gram-negative bacteria that transfers electrons from cytoplasmic thioredoxin to the periplasmic substrate proteins DsbC, DsbG and CcmG, reducing disulfide bonds in the target proteins to dithiols. DsbD consists of three domains: a periplasmic N-terminal domain, a central transmembrane domain and a periplasmic C-terminal domain.

References:

1. Missiakas, D., Schwager, F. and Raina, S. Identification and characterization of a new disulfide isomerase-like protein (DsbD) in Escherichia coli. EMBO J. 14 (1995) 3415-3424. [PMID: 7628442]

2. Gordon, E.H., Page, M.D., Willis, A.C. and Ferguson, S.J. Escherichia coli DipZ: anatomy of a transmembrane protein disulphide reductase in which three pairs of cysteine residues, one in each of three domains, contribute differentially to function. Mol. Microbiol. 35 (2000) 1360-1374. [PMID: 10760137]

3. Katzen, F. and Beckwith, J. Transmembrane electron transfer by the membrane protein DsbD occurs via a disulfide bond cascade. Cell 103 (2000) 769-779. [PMID: 11114333]

4. Goulding, C.W., Sawaya, M.R., Parseghian, A., Lim, V., Eisenberg, D. and Missiakas, D. Thiol-disulfide exchange in an immunoglobulin-like fold: structure of the N-terminal domain of DsbD. Biochemistry 41 (2002) 6920-6927. [PMID: 12033924]

5. Katzen, F. and Beckwith, J. Role and location of the unusual redox-active cysteines in the hydrophobic domain of the transmembrane electron transporter DsbD. Proc. Natl Acad. Sci. USA 100 (2003) 10471-10476. [PMID: 12925743]

6. Rozhkova, A. and Glockshuber, R. Thermodynamic aspects of DsbD-mediated electron transport. J. Mol. Biol. 380 (2008) 783-788. [PMID: 18571669]

[EC 1.8.4.16 created 2019]

EC 1.8.5.9

Accepted name: protein dithiol:quinone oxidoreductase DsbB

Reaction: a [DsbA protein] with reduced L-cysteine residues + a quinone = a [DsbA protein] carrying a disulfide bond + a quinol (overall reaction)
(1a) a [DsbA protein] with reduced L-cysteine residues + a [DsbB protein] carrying a disulfide bond = a [DsbA protein] carrying a disulfide bond + a [DsbB protein] with reduced L-cysteine residues
(1b) a [DsbB protein] with reduced L-cysteine residues + a quinone = a [DsbB protein] carrying a disulfide bond + a quinol

Other name(s): dsbB (gene name)

Systematic name: protein dithiol:quinone oxidoreductase (disulfide-forming)

Comments: DsbB is a protein found in Gram-negative bacteria that functions within a pathway for protein disulfide bond formation. The enzyme catalyses the oxidation of the DsbA protein by generating disulfide bonds de novo via the reduction of membrane quinones. cf. EC 1.8.4.15, protein dithiol oxidoreductase (disulfide-forming)

References:

1. Guilhot, C., Jander, G., Martin, N.L. and Beckwith, J. Evidence that the pathway of disulfide bond formation in Escherichia coli involves interactions between the cysteines of DsbB and DsbA. Proc. Natl Acad. Sci. USA 92 (1995) 9895-9899. [PMID: 7568240]

2. Kishigami, S., Kanaya, E., Kikuchi, M. and Ito, K. DsbA-DsbB interaction through their active site cysteines. Evidence from an odd cysteine mutant of DsbA. J. Biol. Chem 270 (1995) 17072-17074. [PMID: 7615498]

3. Kishigami, S. and Ito, K. Roles of cysteine residues of DsbB in its activity to reoxidize DsbA, the protein disulphide bond catalyst of Escherichia coli. Genes Cells 1 (1996) 201-208. [PMID: 9140064]

4. Collet, J.F. and Bardwell, J.C. Oxidative protein folding in bacteria. Mol. Microbiol. 44 (2002) 1-8. [PMID: 11967064]

5. Dutton, R.J., Boyd, D., Berkmen, M. and Beckwith, J. Bacterial species exhibit diversity in their mechanisms and capacity for protein disulfide bond formation. Proc. Natl Acad. Sci. USA 105 (2008) 11933-11938. [PMID: 18695247]

6. Inaba, K. Disulfide bond formation system in Escherichia coli. J. Biochem. 146 (2009) 591-597. [PMID: 19567379]

[EC 1.8.5.9 created 2019]

[EC 1.9.3.1 Transferred entry: cytochrome-c oxidase. Now EC 7.1.1.9, cytochrome-c oxidase. (EC 1.9.3.1 created 1961, modified 2000, deleted 2019)]

EC 1.10.3.17

Accepted name: superoxide oxidase

Reaction: 2 O2 + ubiquinol = 2 superoxide + ubiquinone + 2 H+

Other name(s): SOO; CybB; cytochrome b561; superoxide:ubiquinone oxidoreductase

Systematic name: ubiquinol:oxygen oxidoreductase (superoxide-forming)

Comments: This membrane-bound, di-heme containing enzyme, identified in the bacterium Escherichia coli, is responsible for the detoxification of superoxide in the periplasm. In vivo the reaction proceeds in the opposite direction of that shown and produces oxygen. Superoxide production was only observed when the enzyme was incubated in vitro with an excess of ubiquinol.

References:

1. Murakami, H., Kita, K. and Anraku, Y. Cloning of cybB, the gene for cytochrome b561 of Escherichia coli K12. Mol. Gen. Genet. 198 (1984) 1-6. [PMID: 6097799]

2. Murakami, H., Kita, K. and Anraku, Y. Purification and properties of a diheme cytochrome b561 of the Escherichia coli respiratory chain. J. Biol. Chem 261 (1986) 548-551. [PMID: 3510204]

3. Lundgren, C.AK., Sjostrand, D., Biner, O., Bennett, M., Rudling, A., Johansson, A.L., Brzezinski, P., Carlsson, J., von Ballmoos, C. and Hogbom, M. Scavenging of superoxide by a membrane-bound superoxide oxidase. Nat. Chem. Biol. 14 (2018) 788-793. [PMID: 29915379]

[EC 1.10.3.17 created 2019]

*EC 1.13.11.79

Accepted name: aerobic 5,6-dimethylbenzimidazole synthase

Reaction: FMNH2 + O2 = 5,6-dimethylbenzimidazole + D-erythrose 4-phosphate + other product(s)

For diagram of reaction click here

Other name(s): BluB; flavin destructase

Systematic name: FMNH2 oxidoreductase (5,6-dimethylbenzimidazole-forming)

Comments: The enzyme catalyses a complex oxygen-dependent conversion of reduced flavin mononucleotide to form 5,6-dimethylbenzimidazole, the lower ligand of vitamin B12. This conversion involves many sequential steps in two distinct stages, and an alloxan intermediate that acts as a proton donor, a proton acceptor, and a hydride acceptor [4]. The C-2 of 5,6-dimethylbenzimidazole is derived from C-1' of the ribityl group of FMNH2 and 2-H from the ribityl 1'-pro-S hydrogen. While D-erythrose 4-phosphate has been shown to be one of the byproducts, the nature of the other product(s) has not been verified yet.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Gray, M.J. and Escalante-Semerena, J.C. Single-enzyme conversion of FMNH2 to 5,6-dimethylbenzimidazole, the lower ligand of B12. Proc. Natl. Acad. Sci. USA 104 (2007) 2921-2926. [PMID: 17301238]

2. Ealick, S.E. and Begley, T.P. Biochemistry: molecular cannibalism. Nature 446 (2007) 387-388. [PMID: 17377573]

3. Taga, M.E., Larsen, N.A., Howard-Jones, A.R., Walsh, C.T. and Walker, G.C. BluB cannibalizes flavin to form the lower ligand of vitamin B12. Nature 446 (2007) 449. [PMID: 17377583]

4. Wang, X.L. and Quan, J.M. Intermediate-assisted multifunctional catalysis in the conversion of flavin to 5,6-dimethylbenzimidazole by BluB: a density functional theory study. J. Am. Chem. Soc. 133 (2011) 4079-4091. [PMID: 21344938]

5. Collins, H.F., Biedendieck, R., Leech, H.K., Gray, M., Escalante-Semerena, J.C., McLean, K.J., Munro, A.W., Rigby, S.E., Warren, M.J. and Lawrence, A.D. Bacillus megaterium has both a functional BluB protein required for DMB synthesis and a related flavoprotein that forms a stable radical species. PLoS One 8 (2013) e55708. [PMID: 23457476]

[EC 1.13.11.79 created 2010 as EC 1.14.99.40, transferred 2014 to EC 1.13.11.79, modified 2019]

EC 1.14.11.70

Accepted name: 7-deoxycylindrospermopsin hydroxylase

Reaction: (1) 7-deoxycylindrospermopsin + 2-oxoglutarate + O2 = cylindrospermopsin + succinate + CO2
(2) 7-deoxycylindrospermopsin + 2-oxoglutarate + O2 = 7-epi-cylindrospermopsin + succinate + CO2

Glossary: cylindrospermopsin = (2aS,3R,4S,5aS,7R)-7-[(R)-(2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)(hydroxy)methyl]-3-methyl-2a,3,4,5,5a,6,7,8-octahydro-2H-1,8,8b-triazaacenaphthylen-4-yl hydrogen sulfate

Other name(s): cyrI (gene name)

Systematic name: 7-deoxycylindrospermopsin, 2-oxoglutarate:oxygen oxidoreductase (7-hydroxylating)

Comments: Requires Fe(II). The enzyme, found in some cyanobacterial species, catalyses the last step in the biosynthesis of the toxins cylindrospermopsin and 7-epi-cylindrospermopsin. The ratio of the two products differs among different strains.

References:

1. Mazmouz, R., Chapuis-Hugon, F., Pichon V., Mejean, A., and Ploux, O. The last step of the biosynthesis of the cyanotoxins cylindrospermopsin and 7-epi-cylindrospermopsin is catalysed by CyrI, a 2-oxoglutarate-dependent iron oxygenase. Chem. Biochem. 12 (2011) 858-862.

2. Mazmouz, R., Essadik, I., Hamdane, D., Mejean, A. and Ploux, O. Characterization of CyrI, the hydroxylase involved in the last step of cylindrospermopsin biosynthesis: Binding studies, site-directed mutagenesis and stereoselectivity. Arch. Biochem. Biophys. 647 (2018) 1-9. [PMID: 29653078]

[EC 1.14.11.70 created 2019]

EC 1.14.11.71

Accepted name: methylphosphonate hydroxylase

Reaction: methylphosphonate + 2-oxoglutarate + O2 = hydroxymethylphosphonate + succinate + CO2

Other name(s): phnY* (gene name)

Systematic name: methylphosphonate,2-oxoglutarate:oxygen oxidoreductase (1-hydroxylating)

Comments: Requires Fe(II). The enzyme, characterized from the marine bacterium Gimesia maris, participates in a methylphosphonate degradation pathway.

References:

1. Gama, S.R., Vogt, M., Kalina, T., Hupp, K., Hammerschmidt, F., Pallitsch, K. and Zechel, D.L. An oxidative pathway for microbial utilization of methylphosphonic acid as a phosphate source. ACS Chem. Biol. 14 (2019) 735-741. [PMID: 30810303]

[EC 1.14.11.71 created 2019]

EC 1.14.13.247

Accepted name: stachydrine N-demethylase

Reaction: L-proline betaine + NAD(P)H + H+ + O2 = N-methyl-L-proline + formaldehyde + NAD(P)+ + H2O

Other name(s): L-proline betaine N-demethylase; stc2 (gene name)

Systematic name: L-proline betaine,NAD(P)H:oxygen oxidoreductase (formaldehyde-forming)

Comments: The enzyme, characterized from the bacterium Sinorhizobium meliloti 1021, consists of three different types of subunits. The catalytic unit contains a Rieske [2Fe-2S] iron-sulfur cluster, and catalyses the monooxygenation of a methyl group. The resulting N-methoxyl group is unstable and decomposes spontaneously to form formaldehyde. The other subunits are involved in the transfer of electrons from NAD(P)H to the catalytic subunit.

References:

1. Daughtry, K.D., Xiao, Y., Stoner-Ma, D., Cho, E., Orville, A.M., Liu, P. and Allen, K.N. Quaternary ammonium oxidative demethylation: X-ray crystallographic, resonance Raman, and UV-visible spectroscopic analysis of a Rieske-type demethylase. J. Am. Chem. Soc. 134 (2012) 2823-2834. [PMID: 22224443]

2. Kumar, R., Zhao, S., Vetting, M.W., Wood, B.M., Sakai, A., Cho, K., Solbiati, J., Almo, S.C., Sweedler, J.V., Jacobson, M.P., Gerlt, J.A. and Cronan, J.E. Prediction and biochemical demonstration of a catabolic pathway for the osmoprotectant proline betaine. MBio 5 (2014) e00933. [PMID: 24520058]

[EC 1.14.13.247 created 2017]

*EC 1.14.14.22

Accepted name: dibenzothiophene sulfone monooxygenase

Reaction: dibenzothiophene-5,5-dioxide + FMNH2 + NADH + O2 = 2'-hydroxybiphenyl-2-sulfinate + H2O + FMN + NAD+ + H+ (overall reaction)
(1a) dibenzothiophene-5,5-dioxide + FMNH2 + O2 = 2'-hydroxybiphenyl-2-sulfinate + FMN-N5-oxide
(1b) FMN-N5-oxide + NADH = FMN + H2O + NAD+ + H+ (spontaneous)

Glossary: dibenzothiophene-5,5-dioxide = dibenzothiophene sulfone

Other name(s): dszA (gene name)

Systematic name: dibenzothiophene-5,5-dioxide,FMNH2:oxygen oxidoreductase

Comments: This bacterial enzyme catalyses a step in the desulfurization pathway of dibenzothiophenes. The enzyme forms a two-component system with a dedicated NADH-dependent FMN reductase (EC 1.5.1.42) encoded by the dszD gene, which also interacts with EC 1.14.14.21, dibenzothiophene monooxygenase. The flavin-N5-oxide that is formed by the enzyme reacts spontaneously with NADH to give oxidized flavin, releasing a water molecule.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Gray, K.A., Pogrebinsky, O.S., Mrachko, G.T., Xi, L., Monticello, D.J. and Squires, C.H. Molecular mechanisms of biocatalytic desulfurization of fossil fuels. Nat. Biotechnol. 14 (1996) 1705-1709. [PMID: 9634856]

2. Ohshiro, T., Kojima, T., Torii, K., Kawasoe, H. and Izumi, Y. Purification and characterization of dibenzothiophene (DBT) sulfone monooxygenase, an enzyme involved in DBT desulfurization, from Rhodococcus erythropolis D-1. J. Biosci. Bioeng. 88 (1999) 610-616. [PMID: 16232672]

3. Konishi, J., Ishii, Y., Onaka, T., Ohta, Y., Suzuki, M. and Maruhashi, K. Purification and characterization of dibenzothiophene sulfone monooxygenase and FMN-dependent NADH oxidoreductase from the thermophilic bacterium Paenibacillus sp. strain A11-2. J. Biosci. Bioeng. 90 (2000) 607-613. [PMID: 16232919]

4. Ohshiro, T., Ishii, Y., Matsubara, T., Ueda, K., Izumi, Y., Kino, K. and Kirimura, K. Dibenzothiophene desulfurizing enzymes from moderately thermophilic bacterium Bacillus subtilis WU-S2B: purification, characterization and overexpression. J. Biosci. Bioeng. 100 (2005) 266-273. [PMID: 16243275]

5. Adak, S. and Begley, T.P. Dibenzothiophene catabolism proceeds via a flavin-N5-oxide intermediate. J. Am. Chem. Soc. 138 (2016) 6424-6426. [PMID: 27120486]

6. Adak, S. and Begley, T.P. Flavin-N5-oxide: A new, catalytic motif in flavoenzymology. Arch. Biochem. Biophys. 632 (2017) 4-10. [PMID: 28784589]

[EC 1.14.14.22 created 2016, modified 2019]

*EC 1.14.16.1

Accepted name: phenylalanine 4-monooxygenase

Reaction: L-phenylalanine + a 5,6,7,8-tetrahydropteridine + O2 = L-tyrosine + a 4a-hydroxy-5,6,7,8-tetrahydropteridine

For diagram of reactions, click here, or click here or click here

Other name(s): phenylalaninase; phenylalanine 4-hydroxylase; phenylalanine hydroxylase

Systematic name: L-phenylalanine,tetrahydropteridine:oxygen oxidoreductase (4-hydroxylating)

Comments: The active centre contains mononuclear iron(II). The reaction involves an arene oxide that rearranges to give the phenolic hydroxy group. This results in the hydrogen at C-4 migrating to C-3 and in part being retained. This process is known as the NIH-shift. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9029-73-6

References:

1. Guroff, G. and Rhoads, C.A. Phenylalanine hydroxylation by Pseudomonas species (ATCC 11299a). Nature of the cofactor. J. Biol. Chem. 244 (1969) 142-146. [PMID: 5773277]

2. Kaufman, S. Studies on the mechanism of the enzymic conversion of phenylalanine to tyrosine. J. Biol. Chem. 234 (1959) 2677-2682. [PMID: 14404870]

3. Mitoma, C. Studies on partially purified phenylalanine hydroxylase. Arch. Biochem. Biophys. 60 (1956) 476-484. [PMID: 13292928]

4. Udenfriend, S. and Cooper, J.R. The enzymic conversion of phenylalanine to tyrosine. J. Biol. Chem. 194 (1952) 503-511. [PMID: 14927641]

5. Carr, R.T., Balasubramanian, S., Hawkins, P.C. and Benkovic, S.J. Mechanism of metal-independent hydroxylation by Chromobacterium violaceum phenylalanine hydroxylase. Biochemistry 34 (1995) 7525-7532. [PMID: 7779797]

6. Andersen, O.A., Flatmark, T. and Hough, E. High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin. J. Mol. Biol. 314 (2001) 266-278. [PMID: 11718561]

7. Erlandsen, H., Kim, J.Y., Patch, M.G., Han, A., Volner, A., Abu-Omar, M.M. and Stevens, R.C. Structural comparison of bacterial and human iron-dependent phenylalanine hydroxylases: similar fold, different stability and reaction rates. J. Mol. Biol. 320 (2002) 645-661. [PMID: 12096915]

[EC 1.14.16.1 created 1961 as EC 1.99.1.2, transferred 1965 to EC 1.14.3.1, transferred 1972 to EC 1.14.16.1, modified 2002, modified 2003, modified 2019]

*EC 1.14.16.2

Accepted name: tyrosine 3-monooxygenase

Reaction: L-tyrosine + a 5,6,7,8-tetrahydropteridine + O2 = L-dopa + a 4a-hydroxy-5,6,7,8-tetrahydropteridine

For diagram of reaction, click here or click here

Glossary: L-dopa = 3,4-dihydroxy-L-phenylalanine

Other name(s): L-tyrosine hydroxylase; tyrosine 3-hydroxylase; tyrosine hydroxylase

Systematic name: L-tyrosine,tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)

Comments: The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by EC 2.7.11.27, [acetyl-CoA carboxylase] kinase. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9036-22-0

References:

1. El Mestikawy, S., Glowinski, J. and Hamon, M. Tyrosine hydroxylase activation in depolarized dopaminergic terminals -involvement of Ca2+-dependent phosphorylation. Nature (Lond.) 302 (1983) 830-832. [PMID: 6133218]

2. Ikeda, M., Levitt, M. and Udenfriend, S. Phenylalanine as substrate and inhibitor of tyrosine hydroxylase. Arch. Biochem. Biophys. 120 (1967) 420-427. [PMID: 6033458]

3. Nagatsu, T., Levitt, M. and Udenfriend, S. Tyrosine hydroxylase. The initial step in norepinephrine biosynthesis. J. Biol. Chem. 239 (1964) 2910-2917. [PMID: 14216443]

4. Pigeon, D., Drissi-Daoudi, R., Gros, F. and Thibault, J. Copurification of tyrosine hydroxylase from rat pheochromocytoma by protein kinase. C. R. Acad. Sci. III 302 (1986) 435-438. [PMID: 2872947]

5. Goodwill, K.E., Sabatier, C., Marks, C., Raag, R., Fitzpatrick, P.F. and Stevens, R.C. Crystal structure of tyrosine hydroxylase at 2.3 Å and its implications for inherited neurodegenerative diseases. Nat. Struct. Biol. 4 (1997) 578-585. [PMID: 9228951]

[EC 1.14.16.2 created 1972, modified 2003, modified 2019]

*EC 1.14.16.4

Accepted name: tryptophan 5-monooxygenase

Reaction: L-tryptophan + a 5,6,7,8-tetrahydropteridine + O2 = 5-hydroxy-L-tryptophan + a 4a-hydroxy-5,6,7,8-tetrahydropteridine

For diagram of reaction click here

Other name(s): L-tryptophan hydroxylase; indoleacetic acid-5-hydroxylase; tryptophan 5-hydroxylase; tryptophan hydroxylase

Systematic name: L-tryptophan,tetrahydropteridine:oxygen oxidoreductase (5-hydroxylating)

Comments: The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by a Ca2+-activated protein kinase. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9037-21-2

References:

1. Friedman, P.A., Kappelman, A.H. and Kaufman, S. Partial purification and characterization of tryptophan hydroxylase from rabbit hindbrain. J. Biol. Chem. 247 (1972) 4165-4173. [PMID: 4402511]

2. Hamon, M., Bourgoin, S., Artaud, F. and Glowinski, J. The role of intraneuronal 5-HT and of tryptophan hydroxylase activation in the control of 5-HT synthesis in rat brain slices incubated in K+-enriched medium. J. Neurochem. 33 (1979) 1031-1042. [PMID: 315449]

3. Ichiyama, A., Nakamura, S., Nishizuka, Y. and Hayaishi, O. Enzymic studies on the biosynthesis of serotonin in mammalian brain. J. Biol. Chem. 245 (1970) 1699-1709. [PMID: 5309585]

4. Jequier, E., Robinson, B.S., Lovenberg, W. and Sjoerdsma, A. Further studies on tryptophan hydroxylase in rat brainstem and beef pineal. Biochem. Pharmacol. 18 (1969) 1071-1081. [PMID: 5789774]

5. Wang, L., Erlandsen, H., Haavik, J., Knappskog, P.M. and Stevens, R.C. Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin. Biochemistry 41 (2002) 12569-12574. [PMID: 12379098]

[EC 1.14.16.4 created 1972, modified 2003, modified 2019]

*EC 1.14.16.7

Accepted name: phenylalanine 3-monooxygenase

Reaction: L-phenylalanine + a 5,6,7,8-tetrahydropteridine + O2 = 3-hydroxy-L-phenylalanine + a 4a-hydroxy-5,6,7,8-tetrahydropteridine

Glossary: 3-hydroxy-L-phenylalanine = meta-L-tyrosine = 3-(3-hydroxyphenyl)-L-alanine

Other name(s): PacX; phenylalanine 3-hydroxylase

Systematic name: L-phenylalanine,tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)

Comments: The enzyme, characterized from the bacterium Streptomyces coeruleorubidus, forms 3-hydroxy-L-phenylalanine (i.e. m-L-tyrosine), which is one of the building blocks in the biosynthesis of the uridyl peptide antibiotics pacidamycins. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Zhang, W., Ames, B.D. and Walsh, C.T. Identification of phenylalanine 3-hydroxylase for meta-tyrosine biosynthesis. Biochemistry 50 (2011) 5401-5403. [PMID: 21615132]

[EC 1.14.16.7 created 2014, modified 2019]

*EC 1.14.17.3

Accepted name: peptidylglycine monooxygenase

Reaction: [peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O

Other name(s): peptidylglycine 2-hydroxylase; peptidyl α-amidating enzyme; peptide-α-amide synthetase; peptide α-amidating enzyme; peptide α-amide synthase; peptidylglycine α-hydroxylase; peptidylglycine α-amidating monooxygenase; PAM-A; PAM-B; PAM; peptidylglycine,ascorbate:oxygen oxidoreductase (2-hydroxylating)

Systematic name: [peptide]-glycine,ascorbate:oxygen oxidoreductase (2-hydroxylating)

Comments: A copper protein. The enzyme binds two copper ions with distinct roles during catalysis. Peptidylglycines with a neutral amino acid residue in the penultimate position are the best substrates for the enzyme. The product is unstable and dismutates to glyoxylate and the corresponding desglycine peptide amide, a reaction catalysed by EC 4.3.2.5 peptidylamidoglycolate lyase. In mammals, the two activities are part of a bifunctional protein. Involved in the final step of biosynthesis of α-melanotropin and related biologically active peptides.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 90597-47-0

References:

1. Bradbury, A.F., Finnie, M.D.A. and Smyth, D.G. Mechanism of C-terminal amide formation by pituitary enzymes. Nature (Lond.) 298 (1982) 686-688. [PMID: 7099265]

2. Glembotski, C.G. Further characterization of the peptidyl α-amidating enzyme in rat anterior pituitary secretory granules. Arch. Biochem. Biophys. 241 (1985) 673-683. [PMID: 2994573]

3. Murthy, A.S.N., Mains, R.E. and Eipper, B.A. Purification and characterization of peptidylglycine α-amidating monooxygenase from bovine neurointermediate pituitary. J. Biol. Chem. 261 (1986) 1815-1822. [PMID: 3944110]

4. Bradbury, A.F. and Smyth, D.G. Enzyme-catalysed peptide amidation. Isolation of a stable intermediate formed by reaction of the amidating enzyme with an imino acid. Eur. J. Biochem. 169 (1987) 579-584. [PMID: 3691506]

5. Murthy, A.S.N., Keutmann, H.T. and Eipper, B.A. Further characterization of peptidylglycine α-amidating monooxygenase from bovine neurointermediate pituitary. Mol. Endocrinol. 1 (1987) 290-299. [PMID: 3453894]

6. Katopodis, A.G., Ping, D. and May, S.W. A novel enzyme from bovine neurointermediate pituitary catalyzes dealkylation of α-hydroxyglycine derivatives, thereby functioning sequentially with peptidylglycine α-amidating monooxygenase in peptide amidation. Biochemistry 29 (1990) 6115-6120. [PMID: 2207061]

7. Prigge, S.T., Kolhekar, A.S., Eipper, B.A., Mains, R.E. and Amzel, L.M. Amidation of bioactive peptides: the structure of peptidylglycine α-hydroxylating monooxygenase. Science 278 (1997) 1300-1305. [PMID: 9360928]

8. Prigge, S.T., Eipper, B.A., Mains, R.E. and Amzel, L.M. Dioxygen binds end-on to mononuclear copper in a precatalytic enzyme complex. Science 304 (2004) 864-867. [PMID: 15131304]

9. Chufan, E.E., Prigge, S.T., Siebert, X., Eipper, B.A., Mains, R.E. and Amzel, L.M. Differential reactivity between two copper sites in peptidylglycine α-hydroxylating monooxygenase. J. Am. Chem. Soc. 132 (2010) 15565-15572. [PMID: 20958070]

10. Chauhan, S., Hosseinzadeh, P., Lu, Y. and Blackburn, N.J. Stopped-flow studies of the reduction of the copper centers suggest a bifurcated electron transfer pathway in peptidylglycine monooxygenase. Biochemistry 55 (2016) 2008-2021. [PMID: 26982589]

[EC 1.14.17.3 created 1989, modified 2019]

*EC 1.14.99.46

Accepted name: pyrimidine oxygenase

Reaction: (1) uracil + FMNH2 + O2 + NADH = (Z)-3-ureidoacrylate + H2O + FMN + NAD+ + H+ (overall reaction)
(1a) uracil + FMNH2 + O2 = (Z)-3-ureidoacrylate + FMN-N5-oxide
(1b) FMN-N5-oxide + NADH = FMN + H2O + NAD+ + H+ (spontaneous)
(2) thymine + FMNH2 + O2 + NADH = (Z)-2-methylureidoacrylate + H2O + FMN + NAD+ + H+ (overall reaction)
(2a) thymine + FMNH2 + O2 = (Z)-2-methylureidoacrylate + FMN-N5-oxide
(2b) FMN-N5-oxide + NADH = FMN + H2O + NAD+ + H+ (spontaneous)

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

Other name(s): rutA (gene name)

Systematic name: uracil,FMNH2:oxygen oxidoreductase (uracil hydroxylating, ring-opening)

Comments: The enzyme participates in the Rut pyrimidine catabolic pathway. The flavin-N5-oxide that is formed by the enzyme reacts spontaneously with NADH to give oxidized flavin, releasing a water molecule.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Mukherjee, T., Zhang, Y., Abdelwahed, S., Ealick, S.E. and Begley, T.P. Catalysis of a flavoenzyme-mediated amide hydrolysis. J. Am. Chem. Soc. 132 (2010) 5550-5551. [PMID: 20369853]

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

3. Adak, S. and Begley, T.P. RutA-catalyzed oxidative cleavage of the uracil amide involves formation of a flavin-N5-oxide. Biochemistry 56 (2017) 3708-3709. [PMID: 28661684]

4. Adak, S. and Begley, T.P. Flavin-N5-oxide: A new, catalytic motif in flavoenzymology. Arch. Biochem. Biophys. 632 (2017) 4-10. [PMID: 28784589]

[EC 1.14.99.46 created 2012, modified 2019]

[EC 1.16.8.1 Deleted entry: cob(II)yrinic acid a,c-diamide reductase. This activity is now known to be catalyzed by EC 2.5.1.17, corrinoid adenosyltransferase (EC 1.16.8.1 created 2004, deleted 2019)]

*EC 2.1.1.74

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

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

Glossary: Ψ = pseudouridine
T = ribothymidine = 5-methyluridine

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

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

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

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 56831-74-4

References:

1. Delk, A.S., Nagle, D.P., Jr. and Rabinowitz, J.C. Methylenetetrahydrofolate-dependent biosynthesis of ribothymidine in transfer RNA of Streptococcus faecalis. Evidence for reduction of the 1-carbon unit by FADH2. J. Biol. Chem. 255 (1980) 4387-4390. [PMID: 6768721]

2. Becker, H.F., Motorin, Y., Sissler, M., Florentz, C. and Grosjean, H. Major identity determinants for enzymatic formation of ribothymidine and pseudouridine in the TΨ-loop of yeast tRNAs. J. Mol. Biol. 274 (1997) 505-518. [PMID: 9417931]

3. Nishimasu, H., Ishitani, R., Yamashita, K., Iwashita, C., Hirata, A., Hori, H. and Nureki, O. Atomic structure of a folate/FAD-dependent tRNA T54 methyltransferase. Proc. Natl. Acad. Sci. USA 106 (2009) 8180-8185. [PMID: 19416846]

4. Yamagami, R., Yamashita, K., Nishimasu, H., Tomikawa, C., Ochi, A., Iwashita, C., Hirata, A., Ishitani, R., Nureki, O. and Hori, H. The tRNA recognition mechanism of folate/FAD-dependent tRNA methyltransferase (TrmFO). J. Biol. Chem 287 (2012) 42480-42494. [PMID: 23095745]

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

EC 2.1.1.363

Accepted name: pre-sodorifen synthase

Reaction: S-adenosyl-L-methionine + (2E,6E)-farnesyl diphosphate = S-adenosyl-L-homocysteine + pre-sodorifen diphosphate

Glossary: pre-sodorifen diphosphate = [(2E)-3-methyl-5-[(1S,4R,5R)-1,2,3,4,5-pentamethylcyclopent-2-en-1-yl]pent-2-en-1-yl phosphonato]oxyphosphonate
sodorifen = (1S,2S,4R,5S,8s)-1,2,4,5,6,7,8-heptamethyl-3-methylenebicyclo[3.2.1]oct-6-ene

Other name(s): sodC (gene name)

Systematic name: (2E,6E)-farnesyl diphosphate 10-C-methyltransferase (cyclyzing, pre-sodorifen diphosphate producing)

Comments: The enzyme, characterized from the bacterium Serratia plymuthica, participates in biosynthesis of sodorifen.

References:

1. Domik, D., Magnus, N. and Piechulla, B. Analysis of a new cluster of genes involved in the synthesis of the unique volatile organic compound sodorifen of Serratia plymuthica 4Rx13. FEMS Microbiol. Lett. 363(14) (2016) fnw139. [PMID: 27231241]

2. Schmidt, R., Jager, V., Zuhlke, D., Wolff, C., Bernhardt, J., Cankar, K., Beekwilder, J., Ijcken, W.V., Sleutels, F., Boer, W., Riedel, K. and Garbeva, P. Fungal volatile compounds induce production of the secondary metabolite sodorifen in Serratia plymuthica PRI-2C. Sci Rep 7 (2017) 862. [PMID: 28408760]

3. von Reuss, S., Domik, D., Lemfack, M.C., Magnus, N., Kai, M., Weise, T. and Piechulla, B. Sodorifen biosynthesis in the rhizobacterium Serratia plymuthica involves methylation and cyclization of MEP-derived farnesyl pyrophosphate by a SAM-dependent C-methyltransferase. J. Am. Chem. Soc. 140 (2018) 11855-11862. [PMID: 30133268]

[EC 2.1.1.363 created 2019]

*EC 2.3.1.291

Accepted name: sphingoid base N-palmitoyltransferase

Reaction: palmitoyl-CoA + a sphingoid base = an N-(palmitoyl)-sphingoid base + CoA

Other name(s): mammalian ceramide synthase 5; CERS5 (gene name); LASS5 (gene name)

Systematic name: palmitoyl-CoA:sphingoid base N-palmitoyltransferase

Comments: Mammals have six ceramide synthases that exhibit relatively strict specificity regarding the chain-length of their acyl-CoA substrates. Ceramide synthase 5 (CERS5) is specific for palmitoyl-CoA as the acyl donor. It can use multiple sphingoid bases including sphinganine, sphingosine, and phytosphingosine.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Lahiri, S. and Futerman, A.H. LASS5 is a bona fide dihydroceramide synthase that selectively utilizes palmitoyl-CoA as acyl donor. J. Biol. Chem 280 (2005) 33735-33738. [PMID: 16100120]

2. Xu, Z., Zhou, J., McCoy, D.M. and Mallampalli, R.K. LASS5 is the predominant ceramide synthase isoform involved in de novo sphingolipid synthesis in lung epithelia. J. Lipid Res. 46 (2005) 1229-1238. [PMID: 15772421]

3. Mizutani, Y., Kihara, A. and Igarashi, Y. Mammalian Lass6 and its related family members regulate synthesis of specific ceramides. Biochem. J. 390 (2005) 263-271. [PMID: 15823095]

[EC 2.3.1.291 created 2019, modified 2019]

EC 2.3.2.33

Accepted name: RCR-type E3 ubiquitin transferase

Reaction: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-threonine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-3-O-ubiquitinyl-L-threonine (overall reaction)
(1a) [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [RCR-type E3 ubiquitin transferase]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [RCR-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine
(1b) [RCR-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-threonine = [RCR-type E3 ubiquitin transferase]-L-cysteine + [acceptor protein]-3-O-ubiquitinyl-L-threonine

Glossary: RCR = RING-Cys-Relay
RING = Really Interesting New Gene

Other name(s): MYCBP2; PHR1

Systematic name: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:acceptor protein ubiquitin transferase (isopeptide bond-forming; RCR-type)

Comments: RCR-type E3 ubiquitin transferases is a class of RING-type E3 ubiquitin transferase (see EC 2.3.2.27) that mediates ubiquitylation of acceptor proteins via an internal cysteine residue. The RING1 domain binds an EC 2.3.2.23, E2 ubiquitin-conjugating enzyme, and transfers the ubiquitin that is bound to it to an internal cysteine residue on a mediator loop of the RCR-type ligase. The ubiquitin may be transferred to a second internal cysteine before the transfer of the ubiquitin from the RCR-type ligase to the substrate.

References:

1. Pao, K.C., Wood, N.T., Knebel, A., Rafie, K., Stanley, M., Mabbitt, P.D., Sundaramoorthy, R., Hofmann, K., van Aalten, D.MF. and Virdee, S. Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity. Nature 556 (2018) 381-385. [PMID: 29643511]

[EC 2.3.2.33 created 2019]

EC 2.4.1.371

Accepted name: polymannosyl GlcNAc-diphospho-ditrans,octacis-undecaprenol 2,3-α-mannosylpolymerase

Reaction: (1) 2 GDP-α-D-mannose + [α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→2)-α-D-Man-(1→2)]n-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol = 2 GDP + α-D-Man-(1→2)-α-D-Man-(1→2)-[α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→2)-α-D-Man-(1→2)]n-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol
(2) 2 GDP-α-D-mannose + α-D-Man-(1→2)-α-D-Man-(1→2)-[α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→2)-α-D-Man-(1→2)]n-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol = 2 GDP + [α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→2)-α-D-Man-(1→2)]n+1-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol

Other name(s): WbdA

Systematic name: GDP-α-D-mannose:α-D-Man-(1→2)-α-D-Man-(1→2)-[α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→2)-α-D-Man-(1→2)]n-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol 2,3-α-mannosyltransferase (configuration-retaining)

Comments: The enzyme is involved in the biosynthesis of polymannose O-polysaccharide in the outer leaflet of the membrane of Escherichia coli serotype O9a. The enzymes consists of two domains that are responsible for the 1→2 and 1→3 linkages, respectively.

References:

1. Greenfield, L.K., Richards, M.R., Li, J., Wakarchuk, W.W., Lowary, T.L. and Whitfield, C. Biosynthesis of the polymannose lipopolysaccharide O-antigens from Escherichia coli serotypes O8 and O9a requires a unique combination of single- and multiple-active site mannosyltransferases. J. Biol. Chem. 287 (2012) 35078-35091. [PMID: 22875852]

2. Greenfield, L.K., Richards, M.R., Vinogradov, E., Wakarchuk, W.W., Lowary, T.L. and Whitfield, C. Domain organization of the polymerizing mannosyltransferases involved in synthesis of the Escherichia coli O8 and O9a lipopolysaccharide O-antigens. J. Biol. Chem. 287 (2012) 38135-38149. [PMID: 22989876]

3. Liston, S.D., Clarke, B.R., Greenfield, L.K., Richards, M.R., Lowary, T.L. and Whitfield, C. Domain interactions control complex formation and polymerase specificity in the biosynthesis of the Escherichia coli O9a antigen. J. Biol. Chem. 290 (2015) 1075-1085. [PMID: 25422321]

[EC 2.4.1.371 created 2019]

EC 2.4.1.372

Accepted name: mutansucrase

Reaction: sucrose + [(1→3)-α-D-glucosyl]n = D-fructose + [(1→3)-α-D-glucosyl]n+1

Other name(s): gtfJ (gene name)

Systematic name: sucrose:(1→3)-α-D-glucan 3-α-D-glucosyltransferase

Comments: The glucansucrases transfer a D-glusosyl residue from sucrose to a glucan chain. They are classified based on the linkage by which they attach the transferred residue. In some cases, in which the enzyme forms more than one linkage type, classification relies on the relative proportion of the linkages that are generated. Currently classified glucansucrases include EC 2.4.1.372, mutansucrase, which extends (1→3)-α-D-glucans; EC 2.4.1.4, amylosucrase, which extends (1→4)-α-D-glucans; EC 2.4.1.5, dextransucrase, which extends (1→6) α-D-glucans; EC 2.4.1.373, α-(1→2) branching sucrase, which introduces α(1→2) branches into (1→6)-α-D-glucans; EC 2.4.1.125, sucrose—1,6-α-glucan 3(6)-α-glucosyltransferase, which extends (1→6) α-D-glucans by both α(1→3) and α(1→6) linkages, with one of the linkage types being dominant; and EC 2.4.1.140, alternansucrase, which forms both α(1→3) and α(1→6) linkages in approximately equal amounts by alternating the linkage type.

References:

1. Simpson, C.L., Cheetham, N.W., Giffard, P.M. and Jacques, N.A. Four glucosyltransferases, GtfJ, GtfK, GtfL and GtfM, from Streptococcus salivarius ATCC 25975. Microbiology 141 (1995) 1451-1460. [PMID: 7545511]

2. Puanglek, S., Kimura, S., Enomoto-Rogers, Y., Kabe, T., Yoshida, M., Wada, M. and Iwata, T. In vitro synthesis of linear α-1,3-glucan and chemical modification to ester derivatives exhibiting outstanding thermal properties. Sci Rep 6 (2016) 30479. [PMID: 27469976]

[EC 2.4.1.372 created 2019]

EC 2.4.1.373

Accepted name: α-(1→2) branching sucrase

Reaction: sucrose + a (1→6)-α-D-glucan = D-fructose + a (1→6)-α-D-glucan containing a (1→2)-α-D-glucose branch

Systematic name: sucrose:(1→6)-α-D-glucan 2-α-D-glucosyl-transferase

Comments: The glucansucrases transfer a D-glusosyl residue from sucrose to a glucan chain. They are classified based on the linkage by which they attach the transferred residue. In some cases, in which the enzyme forms more than one linkage type, classification relies on the relative proportion of the linkages that are generated. Currently classified glucansucrases include EC 2.4.1.372, mutansucrase, which extends (1→3)-α-D-glucans; EC 2.4.1.4, amylosucrase, which extends (1→4)-α-D-glucans; EC 2.4.1.5, dextransucrase, which extends (1→6) α-D-glucans; EC 2.4.1.373, α-(1→2) branching sucrase, which introduces α(1→2) branches into (1→6)-α-D-glucans; EC 2.4.1.125, sucrose—1,6-α-glucan 3(6)-α-glucosyltransferase, which extends (1→6) α-D-glucans by both α(1→3) and α(1→6) linkages, with one of the linkage types being dominant; and EC 2.4.1.140, alternansucrase, which forms both α(1→3) and α(1→6) linkages in approximately equal amounts by alternating the linkage type.

References:

1. Fabre, E., Bozonnet, S., Arcache, A., Willemot, R.M., Vignon, M., Monsan, P. and Remaud-Simeon, M. Role of the two catalytic domains of DSR-E dextransucrase and their involvement in the formation of highly α-1,2 branched dextran. J. Bacteriol. 187 (2005) 296-303. [PMID: 15601714]

2. Brison, Y., Laguerre, S., Lefoulon, F., Morel, S., Monties, N., Potocki-Veronese, G., Monsan, P. and Remaud-Simeon, M. Branching pattern of gluco-oligosaccharides and 1.5kDa dextran grafted by the α-1,2 branching sucrase GBD-CD2. Carbohydr Polym 94 (2013) 567-576. [PMID: 23544576]

3. Passerini, D., Vuillemin, M., Ufarte, L., Morel, S., Loux, V., Fontagne-Faucher, C., Monsan, P., Remaud-Simeon, M. and Moulis, C. Inventory of the GH70 enzymes encoded by Leuconostoc citreum NRRL B-1299 - identification of three novel α-transglucosylases. FEBS J. 282 (2015) 2115-2130. [PMID: 25756290]

[EC 2.4.1.373 created 2019]

EC 2.4.1.374

Accepted name: β-1,2-mannooligosaccharide synthase

Reaction: GDP-α-D-mannose + [(1→2)-β-D-mannosyl]n = GDP + [(1→2)-β-D-mannosyl]n+1

Other name(s): MTP1 (gene name); MTP2 (gene name)

Systematic name: GDP-α-D-mannose:(1→2)-β-D-mannan mannosyltransferase (configuration-inverting)

Comments: The enzyme, characterized from Leishmania parasites, is involved in synthesis of mannogen, a β-1,2-mannan oligosaccharide used by the organisms as a carbohydrate reserve.

References:

1. Sernee, M.F., Ralton, J.E., Nero, T.L., Sobala, L.F., Kloehn, J., Vieira-Lara, M.A., Cobbold, S.A., Stanton, L., Pires, D.EV., Hanssen, E., Males, A., Ward, T., Bastidas, L.M., van der Peet, P.L., Parker, M.W., Ascher, D.B., Williams, S.J., Davies, G.J. and McConville, M.J. A family of dual-activity glycosyltransferase-phosphorylases mediates mannogen turnover and virulence in Leishmania parasites. Cell Host Microbe 26 (2019) 385-399.e9. [PMID: 31513773]

[EC 2.4.1.374 created 2019]

EC 2.6.1.118

Accepted name: [amino group carrier protein]-γ-(L-lysyl)-L-glutamate aminotransferase

Reaction: an [amino group carrier protein]-C-terminal-γ-(L-lysyl)-L-glutamate + 2-oxoglutarate = an [amino group carrier protein]-C-terminal-N-(1-carboxy-5-oxopentan-1-yl)-L-glutamine + L-glutamate

Other name(s): lysJ (gene name)

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

Comments: The enzyme participates in an L-lysine biosynthesis pathway in certain species of archaea and bacteria.

References:

1. Miyazaki, J., Kobashi, N., Nishiyama, M. and Yamane, H. Functional and evolutionary relationship between arginine biosynthesis and prokaryotic lysine biosynthesis through α-aminoadipate. J. Bacteriol. 183 (2001) 5067-5073. [PMID: 11489859]

2. Horie, A., Tomita, T., Saiki, A., Kono, H., Taka, H., Mineki, R., Fujimura, T., Nishiyama, C., Kuzuyama, T. and Nishiyama, M. Discovery of proteinaceous N-modification in lysine biosynthesis of Thermus thermophilus. Nat. Chem. Biol. 5 (2009) 673-679. [PMID: 19620981]

[EC 2.6.1.118 created 2019]

EC 2.7.1.230

Accepted name: amicoumacin kinase

Reaction: ATP + amicoumacin A = ADP + amicoumacin A 2-phosphate

Other name(s): amiN (gene name); yerI (gene name)

Systematic name: ATP:amicoumacin A 2-phosphotransferase

Comments: The enzyme, found in some bacterial species, inactivates the antibiotic amicoumacin A by phosphorylating it, conferring resistance on the bacteria.

References:

1. Terekhov, S.S., Smirnov, I.V., Malakhova, M.V., Samoilov, A.E., Manolov, A.I., Nazarov, A.S., Danilov, D.V., Dubiley, S.A., Osterman, I.A., Rubtsova, M.P., Kostryukova, E.S., Ziganshin, R.H., Kornienko, M.A., Vanyushkina, A.A., Bukato, O.N., Ilina, E.N., Vlasov, V.V., Severinov, K.V., Gabibov, A.G. and Altman, S. Ultrahigh-throughput functional profiling of microbiota communities. Proc. Natl Acad. Sci. USA 115 (2018) 9551-9556. [PMID: 30181282]

[EC 2.7.1.230 created 2019]

EC 2.7.2.16

Accepted name: 2-phosphoglycerate kinase

Reaction: ATP + 2-phospho-D-glycerate = ADP + 2,3-diphospho-D-glycerate

Other name(s): pgk2 (gene name)

Systematic name: ATP:2-phosphoglycerate 3-phosphotransferase

Comments: The enzyme, found in a number of methanogenic archaeal genera, is involved in the biosynthesis of cyclic 2,3-bisphosphoglycerate, a thermoprotectant. Activity is stimulated by potassium ions.

References:

1. Lehmacher, A., Vogt, A.B. and Hensel, R. Biosynthesis of cyclic 2,3-diphosphoglycerate. Isolation and characterization of 2-phosphoglycerate kinase and cyclic 2,3-diphosphoglycerate synthetase from Methanothermus fervidus. FEBS Lett. 272 (1990) 94-98. [PMID: 2226838]

2. Lehmacher, A. and Hensel, R. Cloning, sequencing and expression of the gene encoding 2-phosphoglycerate kinase from Methanothermus fervidus. Mol. Gen. Genet. 242 (1994) 163-168. [PMID: 8159166]

[EC 2.7.2.16 created 2019]

EC 3.1.3.107

Accepted name: amicoumacin phosphatase

Reaction: amicoumacin A 2-phosphate + H2O = amicoumacin A + phosphate

Other name(s): amiO (gene name)

Systematic name: amicoumacin 2-phosphate phosphohydrolase

Comments: This bacterial enzyme activates the antibiotic amicoumacin A by removing a phosphate group that is added by EC 2.7.1.230, amicoumacin kinase.

References:

1. Terekhov, S.S., Smirnov, I.V., Malakhova, M.V., Samoilov, A.E., Manolov, A.I., Nazarov, A.S., Danilov, D.V., Dubiley, S.A., Osterman, I.A., Rubtsova, M.P., Kostryukova, E.S., Ziganshin, R.H., Kornienko, M.A., Vanyushkina, A.A., Bukato, O.N., Ilina, E.N., Vlasov, V.V., Severinov, K.V., Gabibov, A.G. and Altman, S. Ultrahigh-throughput functional profiling of microbiota communities. Proc. Natl Acad. Sci. USA 115 (2018) 9551-9556. [PMID: 30181282]

[EC 3.1.3.107 created 2019]

[EC 3.1.11.7 Transferred entry: adenosine-5-diphospho-5-[DNA] diphosphatase, Now EC 3.6.1.71, adenosine-5-diphospho-5-[DNA] diphosphatase (EC 3.1.11.7 created 2017, deleted 2019)]

[EC 3.1.11.8 Transferred entry: guanosine-5-diphospho-5-[DNA] diphosphatase. Now EC 3.6.1.70, guanosine-5-diphospho-5-[DNA] diphosphatase (EC 3.1.11.8 created 2017, deleted 2019)]

[EC 3.1.12.2 Transferred entry: DNA-3-diphospho-5-guanosine diphosphatase. Now EC 3.6.1.72, DNA-3-diphospho-5-guanosine diphosphatase (EC 3.1.12.2 created 2017, deleted 2019)]

EC 3.6.1.69

Accepted name: 8-oxo-(d)GTP phosphatase

Reaction: (1) 8-oxo-GTP + H2O = 8-oxo-GDP + phosphate
(2) 8-oxo-dGTP + H2O = 8-oxo-dGDP + phosphate

Glossary: 8-oxo-dGTP = 2'-deoxy-7,8-dihydro-8-oxoguanosine 5'-triphosphate

Other name(s): mutT1 (gene name)

Systematic name: 8-oxo-dGTP diphosphohydrolase

Comments: The enzyme, characterized from the bacterium Mycobacterium tuberculosis, catalyses the hydrolysis of both 8-oxo-GTP and 8-oxo-dGTP, thereby preventing transcriptional and translational errors caused by oxidative damage. The enzyme is highly specific. Unlike EC 3.6.1.55, 8-oxo-dGTP diphosphatase, it removes only a single phosphate group. The nucleoside diphosphate products are hydrolysed further by EC 3.6.1.58, 8-oxo-dGDP phosphatase.

References:

1. Patil, A.G., Sang, P.B., Govindan, A. and Varshney, U. Mycobacterium tuberculosis MutT1 (Rv2985) and ADPRase (Rv1700) proteins constitute a two-stage mechanism of 8-oxo-dGTP and 8-oxo-GTP detoxification and adenosine to cytidine mutation avoidance. J. Biol. Chem 288 (2013) 11252-11262. [PMID: 23463507]

[EC 3.6.1.69 created 2019]

EC 3.6.1.70

Accepted name: guanosine-5'-diphospho-5'-[DNA] diphosphatase

Reaction: guanosine-5'-diphospho-5'-[DNA] + H2O = phospho-5'-[DNA] + GMP

Other name(s): aprataxin; pp5'G5'DNA diphosphatase; pp5'G5'-DNA guanylate hydrolase; APTX (gene name); HNT3 (gene name)

Systematic name: guanosine-5'-diphospho-5'-[DNA] hydrolase (guanosine 5'-phosphate-forming)

Comments: Aprataxin is a DNA-binding protein that catalyses (among other activities) the 5' decapping of Gpp-DNA (formed by homologs of RtcB3 from the bacterium Myxococcus xanthus). The enzyme binds the guanylate group to a histidine residue at its active site, forming a covalent enzyme-nucleotide phosphate intermediate, followed by the hydrolysis of the guanylate from the nucleic acid and eventual release. The enzyme forms a 5'-phospho terminus that can be efficiently joined by "classical" ligases. The enzyme also possesses the activitiy of EC 3.6.1.71, adenosine-5'-diphospho-5'-[DNA] diphosphatase and EC 3.6.1.72, DNA-3'-diphospho-5'-guanosine diphosphatase.

References:

1. Maughan, W.P. and Shuman, S. Characterization of 3'-phosphate RNA ligase paralogs RtcB1, RtcB2, and RtcB3 from Myxococcus xanthus highlights DNA and RNA 5'-phosphate capping activity of RtcB3. J. Bacteriol. 197 (2015) 3616-3624. [PMID: 26350128]

[EC 3.6.1.70 created 2017 as EC 3.1.11.8, transferred 2019 to EC 3.6.1.70]

EC 3.6.1.71

Accepted name: adenosine-5'-diphospho-5'-[DNA] diphosphatase

Reaction: (1) adenosine-5'-diphospho-5'-[DNA] + H2O = AMP + phospho-5'-[DNA]
(2) adenosine-5'-diphospho-5'-(ribonucleotide)-[DNA] + H2O = AMP + 5'-phospho-(ribonucleotide)-[DNA]

Other name(s): aprataxin; 5'-App5'-DNA adenylate hydrolase; APTX (gene name); HNT3 (gene name)

Systematic name: adenosine-5'-diphospho-5'-[DNA] hydrolase (adenosine 5'-phosphate-forming)

Comments: Aprataxin is a DNA-binding protein involved in different types of DNA break repair. The enzyme acts (among other activities) on abortive DNA ligation intermediates that contain an adenylate covalently linked to the 5'-phosphate DNA terminus. It also acts when the adenylate is covalently linked to the 5'-phosphate of a ribonucleotide linked to a DNA strand, which is the result of abortive ligase activty on products of EC 3.1.26.4, ribonuclease H, an enzyme that cleaves RNA-DNA hybrids on the 5' side of the ribonucleotide found in the 5'-RNA-DNA-3' junction. Aprataxin binds the adenylate group to a histidine residue within the active site, followed by its hydrolysis from the nucleic acid and eventual release, leaving a 5'-phosphate terminus that can be efficiently rejoined. The enzyme also possesses the activities of EC 3.6.1.70, guanosine-5'-diphospho-5'-[DNA] diphosphatase, and EC 3.6.1.72, DNA-3'-diphospho-5'-guanosine diphosphatase.

References:

1. Ahel, I., Rass, U., El-Khamisy, S.F., Katyal, S., Clements, P.M., McKinnon, P.J., Caldecott, K.W. and West, S.C. The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates. Nature 443 (2006) 713-716. [PMID: 16964241]

2. Tumbale, P., Williams, J.S., Schellenberg, M.J., Kunkel, T.A. and Williams, R.S. Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity. Nature 506 (2014) 111-115. [PMID: 24362567]

[EC 3.6.1.71 created 2017 as EC 3.1.11.7, transferred 2019 to EC 3.6.1.71]

EC 3.6.1.72

Accepted name: DNA-3'-diphospho-5'-guanosine diphosphatase

Reaction: [DNA]-3'-diphospho-5'-guanosine + H2O = [DNA]-3'-phosphate + GMP

Other name(s): aprataxin; DNA-3'pp5'G guanylate hydrolase; APTX (gene name); HNT3 (gene name)

Systematic name: [DNA]-3'-diphospho-5'-guanosine hydrolase (guanosine 5'-phosphate-forming)

Comments: Aprataxin is a DNA-binding protein that catalyses (among other activities) the 3' decapping of DNA-ppG (formed by EC 6.5.1.8, 3'-phosphate/5'-hydroxy nucleic acid ligase) [1]. The enzyme binds the guanylate group to a histidine residue at its active site, forming a covalent enzyme-nucleotide phosphate intermediate, followed by the hydrolysis of the guanylate from the nucleic acid and its eventual release. The enzyme also possesses the activity of EC 3.6.1.71, adenosine-5'-diphospho-5'-[DNA] diphosphatase, and EC 3.6.1.70, guanosine-5'-diphospho-5'-[DNA] diphosphatase.

References:

1. Das, U., Chauleau, M., Ordonez, H. and Shuman, S. Impact of DNA3'pp5'G capping on repair reactions at DNA 3' ends. Proc. Natl. Acad. Sci. USA 111 (2014) 11317-11322. [PMID: 25049385]

2. Chauleau, M., Jacewicz, A. and Shuman, S. DNA3'pp5'G de-capping activity of aprataxin: effect of cap nucleoside analogs and structural basis for guanosine recognition. Nucleic Acids Res. 43 (2015) 6075-6083. [PMID: 26007660]

[EC 3.6.1.72 created 2017 as EC 3.1.12.2, transferred 2019 to EC 3.6.1.72]

EC 4.1.1.119

Accepted name: phenylacetate decarboxylase

Reaction: phenylacetate = toluene + CO2

Other name(s): phdB (gene name)

Systematic name: phenylacetate carboxy-lyase

Comments: This bacterial enzyme, isolated from anoxic, toluene-producing microbial communities, is a glycyl radical enzyme. It needs to be activated by a dedicated activating enzyme (PhdA). The activase catalyses the reductive cleavage of AdoMet, producing a 5'-deoxyadenosyl radical that leads to the production of the glycyl radical in PhdB.

References:

1. Zargar, K., Saville, R., Phelan, R.M., Tringe, S.G., Petzold, C.J., Keasling, J.D. and Beller, H.R. In vitro characterization of phenylacetate decarboxylase, a novel enzyme catalyzing toluene biosynthesis in an anaerobic microbial community. Sci. Rep. 6 (2016) 31362. [PMID: 27506494]

2. Beller, H.R., Rodrigues, A.V., Zargar, K., Wu, Y.W., Saini, A.K., Saville, R.M., Pereira, J.H., Adams, P.D., Tringe, S.G., Petzold, C.J. and Keasling, J.D. Discovery of enzymes for toluene synthesis from anoxic microbial communities. Nat. Chem. Biol. 14 (2018) 451-457. [PMID: 29556105]

3. Rodrigues, A.V., Tantillo, D.J., Mukhopadhyay, A., Keasling, J.D. and Beller, H. Insights into the mechanism of phenylacetate decarboxylase (PhdB), a toluene-producing glycyl radical enzyme. Chembiochem (2019) . [PMID: 31512343]

[EC 4.1.1.119 created 2019]

*EC 4.3.2.5

Accepted name: peptidylamidoglycolate lyase

Reaction: [peptide]-(2S)-2-hydroxyglycine = [peptide]-amide + glyoxylate

Other name(s): α-hydroxyglycine amidating dealkylase; peptidyl-α-hydroxyglycine α-amidating lyase; HGAD; PGL; PAL; peptidylamidoglycolate peptidylamide-lyase

Systematic name: [peptide]-(2S)-2-hydroxyglycine peptidyl-amide-lyase (glyoxylate-forming)

Comments: Requires zinc. The enzyme acts on the product of the reaction catalysed by EC 1.14.17.3 peptidylglycine monooxygenase, thus removing a terminal glycine residue and leaving a des-glycine peptide amide. In mammals, the two activities are part of a bifunctional protein.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 131689-50-4

References:

1. Katapodis, A.G., Ping, D. and May, S.W. A novel enzyme from bovine neurointermediate pituitary catalyzes dealkylation of α-hydroxyglycine derivatives, thereby functioning sequentially with peptidylglycine α-amidating monooxygenase in peptide amidation. Biochemistry 29 (1990) 6115-6120. [PMID: 2207061]

2. Bell, J., Ash, D.E., Snyder, L.M., Kulathila, R., Blackburn, N.J. and Merkler, D.J. Structural and functional investigations on the role of zinc in bifunctional rat peptidylglycine α-amidating enzyme. Biochemistry 36 (1997) 16239-16246. [PMID: 9405058]

[EC 4.3.2.5 created 1992, modified 2019]

EC 5.5.1.34

Accepted name: (+)-cis,trans-nepetalactol synthase

Reaction: (S)-8-oxocitronellyl enol = (+)-cis,trans-nepetalactol

For diagram of reaction click here.

Glossary: (S)-8-oxocitronellyl enol = (2E,6S,7E)-8-hydroxy-2,6-dimethylocta-2,7-dienal
(+)-cis,trans-nepetalactol = (+)-iridodial lactol = (4aS,7S,7aR)-4,7-dimethyl-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-1-ol

Other name(s): NEPS1 (gene name); NEPS2 (gene name)

Systematic name: (S)-8-oxocitronellyl enol cyclase [(+)-cis,trans-nepetalactol-forming]

Comments: The enzyme, characterized from the plant Nepeta mussinii, binds an NAD+ cofactor. The product is a precursor of (+)-cis,trans-nepetalactone, the primary ingredient responsible for the psychoactive effects catnip has on cats.

References:

1. Lichman, B.R., Kamileen, M.O., Titchiner, G.R., Saalbach, G., Stevenson, C.EM., Lawson, D.M. and O'Connor, S.E. Uncoupled activation and cyclization in catmint reductive terpenoid biosynthesis. Nat. Chem. Biol. 15 (2019) 71-79. [PMID: 30531909]

2. Lichman, B.R., O'Connor, S.E. and Kries, H. Biocatalytic strategies towards [4+2] cycloadditions. Chemistry 25 (2019) 6864-6877. [PMID: 30664302]

[EC 5.5.1.34 created 2019]

EC 5.5.1.35>

Accepted name: (+)-cis,cis-nepetalactol synthase

Reaction: (S)-8-oxocitronellyl enol = (+)-cis,cis-nepetalactol

For diagram of reaction click here.

Glossary: (S)-8-oxocitronellyl enol = (2E,6S,7E)-8-hydroxy-2,6-dimethylocta-2,7-dienal
(+)-cis,cis-nepetalactol =(4aR,7S,7aS)-4,7-dimethyl-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-1-ol

Other name(s): NEPS3 (gene name)

Systematic name: (S)-8-oxocitronellyl enol cyclase [(+)-cis,cis-nepetalactol-forming]

Comments: The enzyme, characterized from the plant Nepeta mussinii, binds an NAD+ cofactor. The product is a precursor of (+)-cis,cis-nepetalactone, one of the stereoisomers responsible for the psychoactive effects catnip has on cats.

References:

1. Lichman, B.R., Kamileen, M.O., Titchiner, G.R., Saalbach, G., Stevenson, C.EM., Lawson, D.M. and O'Connor, S.E. Uncoupled activation and cyclization in catmint reductive terpenoid biosynthesis. Nat. Chem. Biol. 15 (2019) 71-79. [PMID: 30531909]

2. Lichman, B.R., O'Connor, S.E. and Kries, H. Biocatalytic strategies towards [4+2] cycloadditions. Chemistry 25 (2019) 6864-6877. [PMID: 30664302]

[EC 5.5.1.35 created 2019]

EC 6.2.1.61

Accepted name: salicylate—[aryl-carrier protein] ligase

Reaction: ATP + salicylate + holo-[non-ribosomal peptide synthase] = AMP + diphosphate + salicyl-[non-ribosomal peptide synthase] (overall reaction)
(1a) ATP + salicylate = diphosphate + (salicyl)adenylate
(1b) (salicyl)adenylate + holo-[non-ribosomal peptide synthase] = AMP + salicyl-[non-ribosomal peptide synthase]

Other name(s): pmsE (gene name); pchD (gene name)

Systematic name: salicylate:holo-[non-ribosomal peptide synthase] ligase

Comments: The enzyme catalyses the activation of salicylate to (salicyl)adenylate, followed by the transfer of the activated compound to the free thiol of a phosphopantetheine arm of an aryl-carrier protein, which is often a domain of a larger non-ribosimal peptide synthase. The PmsE enzyme is involved in pseudomonine biosynthesis and transfers the activated salicylate first to itself, and then to a PmsG protein. The PchD enzyme is involved in pyochelin biosynthesis and transfers the activated salicylate directly to the PchE protein.

References:

1. Quadri, L.E., Keating, T.A., Patel, H.M. and Walsh, C.T. Assembly of the Pseudomonas aeruginosa nonribosomal peptide siderophore pyochelin: In vitro reconstitution of aryl-4, 2-bisthiazoline synthetase activity from PchD, PchE, and PchF. Biochemistry 38 (1999) 14941-14954. [PMID: 10555976]

2. Sattely, E.S. and Walsh, C.T. A latent oxazoline electrophile for N-O-C bond formation in pseudomonine biosynthesis. J. Am. Chem. Soc. 130 (2008) 12282-12284. [PMID: 18710233]

[EC 6.2.1.61 created 2019]

*EC 6.3.2.43

Accepted name: [amino group carrier protein]—L-2-aminoadipate ligase

Reaction: ATP + an [amino group carrier protein]-C-terminal-L-glutamate + L-2-aminoadipate = ADP + phosphate + an [amino group carrier protein]-C-terminal-N-(1,5-dicarboxypentan-1-yl)-L-glutamine

Other name(s): α-aminoadipate-lysW ligase lysX (gene name); LysX (ambiguous); AAA—LysW ligase; [lysine-biosynthesis-protein LysW]-C-terminal-L-glutamate:L-2-aminoadipate ligase (ADP-forming); [lysine-biosynthesis-protein LysW]—L-2-aminoadipate ligase

Systematic name: [amino group carrier protein]-C-terminal-L-glutamate:L-2-aminoadipate ligase (ADP-forming)

Comments: The enzymes from the thermophilic bacterium Thermus thermophilus and the thermophilic archaea Sulfolobus acidocaldarius and Sulfolobus tokodaii protect the amino group of L-2-aminoadipate by conjugation to the carrier protein LysW. This reaction is part of the lysine biosynthesis pathway in these organisms.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Vassylyeva, M.N., Sakai, H., Matsuura, T., Sekine, S., Nishiyama, M., Terada, T., Shirouzu, M., Kuramitsu, S., Vassylyev, D.G. and Yokoyama, S. Cloning, expression, purification, crystallization and initial crystallographic analysis of the lysine-biosynthesis LysX protein from Thermus thermophilus HB8. Acta Crystallogr. D Biol. Crystallogr. 59 (2003) 1651-1652. [PMID: 12925802]

2. Horie, A., Tomita, T., Saiki, A., Kono, H., Taka, H., Mineki, R., Fujimura, T., Nishiyama, C., Kuzuyama, T. and Nishiyama, M. Discovery of proteinaceous N-modification in lysine biosynthesis of Thermus thermophilus. Nat. Chem. Biol. 5 (2009) 673-679. [PMID: 19620981]

3. 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. [PMID: 23434852]

[EC 6.3.2.43 created 2014, modified 2019]

*EC 6.3.2.52

Accepted name: jasmonoyl—L-amino acid ligase

Reaction: ATP + jasmonate + an L-amino acid = AMP + diphosphate + a jasmonoyl-L-amino acid

Other name(s): JAR1 (gene name); JAR4 (gene name); JAR6 (gene name); jasmonoyl—L-amino acid synthetase

Systematic name: jasmonate:L-amino acid ligase

Comments: Two jasmonoyl-L-amino acid synthetases have been described from Nicotiana attenuata [3] and one from Arabidopsis thaliana [1]. The N. attenuata enzymes generate jasmonoyl-L-isoleucine, jasmonoyl-L-leucine, and jasmonoyl-L-valine. The enzyme from A. thaliana could catalyse the addition of many different amino acids to jasmonate in vitro [1,4,5]. While the abundant form of jasmonate in plants is (-–-jasmonate, the active form of jasmonoyl-L-isoleucine is (+)-7-iso-jasmonoyl-L-isoleucine.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Staswick, P.E. and Tiryaki, I. The oxylipin signal jasmonic acid is activated by an enzyme that conjugates it to isoleucine in Arabidopsis. Plant Cell 16 (2004) 2117-2127. [PMID: 15258265]

2. Kang, J.H., Wang, L., Giri, A. and Baldwin, I.T. Silencing threonine deaminase and JAR4 in Nicotiana attenuata impairs jasmonic acid-isoleucine-mediated defenses against Manduca sexta. Plant Cell 18 (2006) 3303-3320. [PMID: 17085687]

3. Wang, L., Halitschke, R., Kang, J.H., Berg, A., Harnisch, F. and Baldwin, I.T. Independently silencing two JAR family members impairs levels of trypsin proteinase inhibitors but not nicotine. Planta 226 (2007) 159-167. [PMID: 17273867]

4. Guranowski, A., Miersch, O., Staswick, P.E., Suza, W. and Wasternack, C. Substrate specificity and products of side-reactions catalyzed by jasmonate:amino acid synthetase (JAR1). FEBS Lett. 581 (2007) 815-820. [PMID: 17291501]

5. Suza, W.P. and Staswick, P.E. The role of JAR1 in jasmonoyl-L-isoleucine production during Arabidopsis wound response. Planta 227 (2008) 1221-1232. [PMID: 18247047]

[EC 6.3.2.52 created 2018, modified 2019]

EC 7.1.1.9

Accepted name: cytochrome-c oxidase

Reaction: 4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O

Other name(s): cytochrome aa3; cytochrome caa3; cytochrome bb3; cytochrome cbb3; cytochrome ba3; cytochrome a3; Warburg’s respiratory enzyme; indophenol oxidase; indophenolase; complex IV (mitochondrial electron transport); ferrocytochrome c oxidase; cytochrome oxidase (ambiguous); NADH cytochrome c oxidase (incorrect)

Systematic name: ferrocytochrome-c:oxygen oxidoreductase

Comments: An oligomeric membrane heme-Cu: O2 reductase-type enzyme that terminates the respiratory chains of aerobic and facultative aerobic organisms. The reduction of O2 to water is accompanied by the extrusion of four protons. The cytochrome-aa3 enzymes of mitochondria and many bacterial species are the most abundant group, but other variations, such as the bacterial cytochrome-cbb3 enzymes, also exist. All of the variants have a conserved catalytic core subunit (subunit I) that contains a low-spin heme (of a- or b-type), a binuclear metal centre composed of a high-spin heme iron (of a-, o-, or b-type heme, referred to as a3, o3 or b3 heme), and a Cu atom (CuB). Besides subunit I, the enzyme usually has at least two other core subunits: subunit II is the primary electron acceptor; subunit III usually does not contain any cofactors, but in the case of cbb3-type enzymes it is a diheme c-type cytochrome. While most bacterial enzymes consist of only 3-4 subunits, the mitochondrial enzyme is much more complex and contains 14 subunits.

References:

1. Keilin, D. and Hartree, E.F. Cytochrome oxidase. Proc. R. Soc. Lond. B Biol. Sci. 125 (1938) 171-186.

2. Keilin, D. and Hartree, E.F. Cytochrome and cytochrome oxidase. Proc. R. Soc. Lond. B Biol. Sci. 127 (1939) 167-191.

3. Wainio, W.W., Eichel, B. and Gould, A. Ion and pH optimum for the oxidation of ferrocytochrome c by cytochrome c oxidase in air. J. Biol. Chem. 235 (1960) 1521-1525.

4. Yonetani, T. Studies on cytochrome oxidase. II. Steady state properties. J. Biol. Chem. 235 (1960) 3138-3243. [PMID: 13787372]

5. Yonetani, T. Studies on cytochrome oxidase. III. Improved purification and some properties. J. Biol. Chem. 236 (1961) 1680-1688. [PMID: 13787373]

[EC 7.1.1.9 created 1961 as EC 1.9.3.1, modified 2000, transferred 2019 to EC 7.1.1.9]

EC 7.4.2.13

Accepted name: ABC-type tyrosine transporter

Reaction: ATP + H2O + L-tyrosinyl-[tyrosine-binding protein][side 1] = ADP + phosphate + L-tyrosine[side 2] + [tyrosine-binding protein][side 1]

Systematic name: ATP phosphohydrolase (ABC-type, L-tyrosine-importing)

Comments: An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. The enzyme, found in Clostridioides, interacts with an extracytoplasmic substrate binding lipoprotein and mediates the import of L-tyrosine. L-phenylalanine is also tranported however with lower efficiency.

References:

1. Steglich, M., Hofmann, J.D., Helmecke, J., Sikorski, J., Sproer, C., Riedel, T., Bunk, B., Overmann, J., Neumann-Schaal, M. and Nubel, U. Convergent loss of ABC transporter genes from Clostridioides difficile genomes Is associated with impaired tyrosine uptake and p-cresol production. Front Microbiol 9 (2018) 901. [PMID: 29867812]

[EC 7.4.2.13 created 2019]


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