Proposed Changes to the Enzyme List

References:

1.	Strauss, G. and Fuchs, G. Enzymes of a novel autotrophic CO₂ fixation pathway in the phototrophic bacterium Chloroflexus aurantiacus, the 3-hydroxypropionate cycle. Eur. J. Biochem. 215 (1993) 633–643. [DOI] [PMID: 8354269]
2.	Berg, I.A., Kockelkorn, D., Buckel, W. and Fuchs, G. A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea. Science 318 (2007) 1782–1786. [DOI] [PMID: 18079405]
3.	Hugler, M., Menendez, C., Schagger, H. and Fuchs, G. Malonyl-coenzyme A reductase from Chloroflexus aurantiacus, a key enzyme of the 3-hydroxypropionate cycle for autotrophic CO₂ fixation. J. Bacteriol. 184 (2002) 2404–2410. [DOI] [PMID: 11948153]

[EC 1.1.1.298 created 2009]

1.1.1.299

Accepted name:

malate dehydrogenase [NAD(P)⁺]

Reaction:

(S)-malate + NAD(P)⁺ = oxaloacetate + NAD(P)H + H⁺

Other name(s):

MdH II, NAD(P)⁺-dependent malate dehyrogenase

Systematic name:

(S)-malate:NAD(P)⁺ oxidoreductase

Comments:

This enzyme, which was characterized from the methanogenic archaeon Methanobacterium thermoautotrophicum, catalyses only the reduction of oxaloacetate, and can use NAD⁺ and NADP⁺ with similar specific activity [1]. Different from EC 1.1.1.37 (malate dehydrogenase (NAD⁺)), EC 1.1.1.82 (malate dehydrogenase (NADP⁺)) and EC 1.1.5.4 (malate dehydrogenase (quinone)).

Links to other databases:

References:

1.	Thompson, H., Tersteegen, A., Thauer, R.K. and Hedderich, R. Two malate dehydrogenases in Methanobacterium thermoautotrophicum. Arch. Microbiol. 170 (1998) 38–42. [PMID: 9639601]

[EC 1.1.1.299 created 2009]

1.1.1.300

Accepted name:

NADP-retinol dehydrogenase

Reaction:

retinol + NADP⁺ = retinal + NADPH + H⁺

Other name(s):

all-trans retinal reductase (ambiguous); all-trans-retinol dehydrogenase; NADP(H)-dependent retinol dehydrogenase/reductase; RDH11; RDH12; RDH13; RDH14; retinol dehydrogenase 12; retinol dehydrogenase 14; retinol dehydrogenase [NADP⁺]; RalR1; PSDR1

Systematic name:

retinol:NADP⁺ oxidoreductase

Comments:

Greater catalytic efficiency in the reductive direction. This observation, and the enzyme’s localization at the entrance to the mitochondrial matrix, suggest that it may function to protect mitochondria against oxidative stress associated with the highly reactive retinal produced from dietary β-carotene by EC 1.13.11.63 (β-carotene 15,15′-dioxygenase) [2]. K_m-values for NADP⁺ and NADPH are at least 800-fold lower than those for NAD⁺ and NADH [1,4]. This enzyme differs from EC 1.1.1.105, retinol dehydrogenase, which prefers NAD⁺ and NADH.

Links to other databases:

References:

1.	Belyaeva, O.V., Korkina, O.V., Stetsenko, A.V., Kim, T., Nelson, P.S. and Kedishvili, N.Y. Biochemical properties of purified human retinol dehydrogenase 12 (RDH12): catalytic efficiency toward retinoids and C₉ aldehydes and effects of cellular retinol-binding protein type I (CRBPI) and cellular retinaldehyde-binding protein (CRALBP) on the oxidation and reduction of retinoids. Biochemistry 44 (2005) 7035–7047. [DOI] [PMID: 15865448]
2.	Belyaeva, O.V., Korkina, O.V., Stetsenko, A.V. and Kedishvili, N.Y. Human retinol dehydrogenase 13 (RDH13) is a mitochondrial short-chain dehydrogenase/reductase with a retinaldehyde reductase activity. FEBS J. 275 (2008) 138–147. [DOI] [PMID: 18039331]
3.	Haeseleer, F., Huang, J., Lebioda, L., Saari, J.C. and Palczewski, K. Molecular characterization of a novel short-chain dehydrogenase/reductase that reduces all-trans-retinal. J. Biol. Chem. 273 (1998) 21790–21799. [DOI] [PMID: 9705317]
4.	Kedishvili, N.Y., Chumakova, O.V., Chetyrkin, S.V., Belyaeva, O.V., Lapshina, E.A., Lin, D.W., Matsumura, M. and Nelson, P.S. Evidence that the human gene for prostate short-chain dehydrogenase/reductase (PSDR1) encodes a novel retinal reductase (RalR1). J. Biol. Chem. 277 (2002) 28909–28915. [DOI] [PMID: 12036956]

[EC 1.1.1.300 created 2009]

1.1.5.4

Accepted name:

malate dehydrogenase (quinone)

Reaction:

(S)-malate + a quinone = oxaloacetate + reduced quinone

Other name(s):

FAD-dependent malate-vitamin K reductase; malate-vitamin K reductase; (S)-malate:(acceptor) oxidoreductase; L-malate-quinone oxidoreductase; malate:quinone oxidoreductase; malate quinone oxidoreductase; MQO; malate:quinone reductase; malate dehydrogenase (acceptor); FAD-dependent malate dehydrogenase

Systematic name:

(S)-malate:quinone oxidoreductase

Comments:

A flavoprotein (FAD). Vitamin K and several other quinones can act as acceptors. Different from EC 1.1.1.37 (malate dehydrogenase (NAD⁺)), EC 1.1.1.82 (malate dehydrogenase (NADP⁺)) and EC 1.1.1.299 (malate dehydrogenase [NAD(P)⁺]).

Links to other databases:

References:

1.	Imai, D. and Brodie, A.F. A phospholipid-requiring enzyme, malate-vitamin K reductase. J. Biol. Chem. 248 (1973) 7487–7494.
2.	Imai, T. FAD-dependent malate dehydrogenase, a phospholipid-requiring enzyme from Mycobacterium sp. strain Takeo. Purification and some properties. Biochim. Biophys. Acta 523 (1978) 37–46. [DOI] [PMID: 629992]
3.	Reddy, T.L.P., Suryanarayana, P.M. and Venkitasubramanian, T.A. Variations in the pathways of malate oxidation and phosphorylation in different species of Mycobacteria. Biochim. Biophys. Acta 376 (1975) 210–218. [DOI] [PMID: 234747]
4.	Molenaar, D., van der Rest, M.E. and Petrovic, S. Biochemical and genetic characterization of the membrane-associated malate dehydrogenase (acceptor) from Corynebacterium glutamicum. Eur. J. Biochem. 254 (1998) 395–403. [DOI] [PMID: 9660197]
5.	Kather, B., Stingl, K., van der Rest, M.E., Altendorf, K. and Molenaar, D. Another unusual type of citric acid cycle enzyme in Helicobacter pylori: the malate:quinone oxidoreductase. J. Bacteriol. 182 (2000) 3204–3209. [DOI] [PMID: 10809701]

[EC 1.1.5.4 created 1978 as EC 1.1.99.16, transferred 2009 to EC 1.1.5.4]

1.1.5.5

Accepted name:

alcohol dehydrogenase (quinone)

Reaction:

ethanol + ubiquinone = acetaldehyde + ubiquinol

Other name(s):

type III ADH; membrane associated quinohaemoprotein alcohol dehydrogenase

Systematic name:

alcohol:quinone oxidoreductase

Comments:

Only described in acetic acid bacteria where it is involved in acetic acid production. Associated with membrane. Electron acceptor is membrane ubiquinone. A model structure suggests that, like all other quinoprotein alcohol dehydrogenases, the catalytic subunit has an 8-bladed ‘propeller’ structure, a calcium ion bound to the PQQ in the active site and an unusual disulfide ring structure in close proximity to the PQQ; the catalytic subunit also has a heme c in the C-terminal domain. The enzyme has two additional subunits, one of which contains three molecules of heme c. It does not require amines for activation. It has a restricted substrate specificity, oxidizing a few primary alcohols (C₂ to C₆), but not methanol, secondary alcohols and some aldehydes. It is assayed with phenazine methosulfate or with ferricyanide.

Links to other databases:

References:

1.	Gomez-Manzo, S., Contreras-Zentella, M., Gonzalez-Valdez, A., Sosa-Torres, M., Arreguin-Espinoza, R. and Escamilla-Marvan, E. The PQQ-alcohol dehydrogenase of Gluconacetobacter diazotrophicus. Int. J. Food Microbiol. 125 (2008) 71–78. [DOI] [PMID: 18321602]
2.	Shinagawa, E., Toyama, H., Matsushita, K., Tuitemwong, P., Theeragool, G. and Adachi, O. A novel type of formaldehyde-oxidizing enzyme from the membrane of Acetobacter sp. SKU 14. Biosci. Biotechnol. Biochem. 70 (2006) 850–857. [DOI] [PMID: 16636451]
3.	Chinnawirotpisan, P., Theeragool, G., Limtong, S., Toyama, H., Adachi, O.O. and Matsushita, K. Quinoprotein alcohol dehydrogenase is involved in catabolic acetate production, while NAD-dependent alcohol dehydrogenase in ethanol assimilation in Acetobacter pasteurianus SKU1108. J. Biosci. Bioeng. 96 (2003) 564–571. [DOI] [PMID: 16233574]
4.	Frebortova, J., Matsushita, K., Arata, H. and Adachi, O. Intramolecular electron transport in quinoprotein alcohol dehydrogenase of Acetobacter methanolicus: a redox-titration stud. Biochim. Biophys. Acta 1363 (1998) 24–34. [DOI] [PMID: 9526036]
5.	Matsushita, K., Kobayashi, Y., Mizuguchi, M., Toyama, H., Adachi, O., Sakamoto, K. and Miyoshi, H. A tightly bound quinone functions in the ubiquinone reaction sites of quinoprotein alcohol dehydrogenase of an acetic acid bacterium, Gluconobacter suboxydans. Biosci. Biotechnol. Biochem. 72 (2008) 2723–2731. [DOI] [PMID: 18838797]
6.	Matsushita, K., Yakushi, T., Toyama, H., Shinagawa, E. and Adachi, O. Function of multiple heme c moieties in intramolecular electron transport and ubiquinone reduction in the quinohemoprotein alcohol dehydrogenase-cytochrome c complex of Gluconobacter suboxydans. J. Biol. Chem. 271 (1996) 4850–4857. [DOI] [PMID: 8617755]
7.	Matsushita, K., Takaki, Y., Shinagawa, E., Ameyama, M. and Adachi, O. Ethanol oxidase respiratory chain of acetic acid bacteria. Reactivity with ubiquinone of pyrroloquinoline quinone-dependent alcohol dehydrogenases purified from Acetobacter aceti and Gluconobacter suboxydans. Biosci. Biotechnol. Biochem. 56 (1992) 304–310.
8.	Matsushita, K., Toyama, H. and Adachi, O. Respiratory chains and bioenergetics of acetic acid bacteria. Adv. Microb. Physiol. 36 (1994) 247–301. [PMID: 7942316]
9.	Cozier, G.E., Giles, I.G. and Anthony, C. The structure of the quinoprotein alcohol dehydrogenase of Acetobacter aceti modelled on that of methanol dehydrogenase from Methylobacterium extorquens. Biochem. J. 308 (1995) 375–379. [PMID: 7772016]

[EC 1.1.5.5 created 2009, modified 2010]

1.1.99.16

Transferred entry:

malate dehydrogenase (acceptor). As the acceptor is now known, the enzyme has been transferred to EC 1.1.5.4, malate dehydrogenase (quinone).

[EC 1.1.99.16 created 1978, deleted 2009]

1.2.1.75

Accepted name:

malonyl-CoA reductase (malonate semialdehyde-forming)

Reaction:

malonate semialdehyde + CoA + NADP⁺ = malonyl-CoA + NADPH + H⁺

For diagram of the 3-hydroxypropanoate cycle, click here and for diagram of the 3-hydroxypropanoate/4-hydroxybutanoate cycle and dicarboxylate/4-hydroxybutanoate cycle in archaea, click here

Other name(s):

NADP-dependent malonyl CoA reductase; malonyl CoA reductase (NADP); malonyl CoA reductase (malonate semialdehyde-forming)

Systematic name:

malonate semialdehyde:NADP⁺ oxidoreductase (malonate semialdehyde-forming)

Comments:

Requires Mg²⁺. Catalyses the reduction of malonyl-CoA to malonate semialdehyde, a key step in the 3-hydroxypropanoate and the 3-hydroxypropanoate/4-hydroxybutanoate cycles, autotrophic CO₂ fixation pathways found in some green non-sulfur phototrophic bacteria and some thermoacidophilic archaea, respectively [1,2]. The enzyme from Sulfolobus tokodaii has been purified, and found to contain one RNA molecule per two subunits [3]. The enzyme from Chloroflexus aurantiacus is bifunctional, and also catalyses the next reaction in the pathway, EC 1.1.1.298 [3-hydroxypropionate dehydrogenase (NADP⁺)] [4].

Links to other databases:

References:

1.	Strauss, G. and Fuchs, G. Enzymes of a novel autotrophic CO₂ fixation pathway in the phototrophic bacterium Chloroflexus aurantiacus, the 3-hydroxypropionate cycle. Eur. J. Biochem. 215 (1993) 633–643. [DOI] [PMID: 8354269]
2.	Berg, I.A., Kockelkorn, D., Buckel, W. and Fuchs, G. A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea. Science 318 (2007) 1782–1786. [DOI] [PMID: 18079405]
3.	Alber, B., Olinger, M., Rieder, A., Kockelkorn, D., Jobst, B., Hugler, M. and Fuchs, G. Malonyl-coenzyme A reductase in the modified 3-hydroxypropionate cycle for autotrophic carbon fixation in archaeal Metallosphaera and Sulfolobus spp. J. Bacteriol. 188 (2006) 8551–8559. [DOI] [PMID: 17041055]
4.	Hugler, M., Menendez, C., Schagger, H. and Fuchs, G. Malonyl-coenzyme A reductase from Chloroflexus aurantiacus, a key enzyme of the 3-hydroxypropionate cycle for autotrophic CO₂ fixation. J. Bacteriol. 184 (2002) 2404–2410. [DOI] [PMID: 11948153]

[EC 1.2.1.75 created 2009]

1.2.1.76

Accepted name:

succinate-semialdehyde dehydrogenase (acylating)

Reaction:

succinate semialdehyde + CoA + NADP⁺ = succinyl-CoA + NADPH + H⁺

For diagram of the 3-hydroxypropanoate/4-hydroxybutanoate cycle and dicarboxylate/4-hydroxybutanoate cycle in archaea, click here

Other name(s):

succinyl-coA reductase; coenzyme-A-dependent succinate-semialdehyde dehydrogenase

Systematic name:

succinate semialdehyde:NADP⁺ oxidoreductase (CoA-acylating)

Comments:

Catalyses the NADPH-dependent reduction of succinyl-CoA to succinate semialdehyde. The enzyme has been described in Clostridium kluyveri, where it participates in succinate fermentation [1], and in Metallosphaera sedula, where it participates in the 3-hydroxypropanonate/4-hydroxybutanoate cycle, an autotrophic CO₂ fixation pathway found in some thermoacidophilic archaea [2,3].

Links to other databases:

References:

1.	Sohling, B. and Gottschalk, G. Purification and characterization of a coenzyme-A-dependent succinate-semialdehyde dehydrogenase from Clostridium kluyveri. Eur. J. Biochem. 212 (1993) 121–127. [DOI] [PMID: 8444151]
2.	Alber, B., Olinger, M., Rieder, A., Kockelkorn, D., Jobst, B., Hugler, M. and Fuchs, G. Malonyl-coenzyme A reductase in the modified 3-hydroxypropionate cycle for autotrophic carbon fixation in archaeal Metallosphaera and Sulfolobus spp. J. Bacteriol. 188 (2006) 8551–8559. [DOI] [PMID: 17041055]
3.	Berg, I.A., Kockelkorn, D., Buckel, W. and Fuchs, G. A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea. Science 318 (2007) 1782–1786. [DOI] [PMID: 18079405]

[EC 1.2.1.76 created 2009]

1.3.1.84

Accepted name:

acrylyl-CoA reductase (NADPH)

Reaction:

propanoyl-CoA + NADP⁺ = acryloyl-CoA + NADPH + H⁺

For diagram of the 3-hydroxypropanoate cycle, click here, for diagram of the 3-hydroxypropanoate/4-hydroxybutanoate cycle and dicarboxylate/4-hydroxybutanoate cycle in archaea, click here and for diagram of 3-(dimethylsulfonio)propanoate met

Glossary:

propanoyl-CoA = propionyl-CoA
acryloyl-CoA = acrylyl-CoA = propenoyl-CoA

Systematic name:

propanoyl-CoA:NADP⁺ oxidoreductase

Comments:

Catalyses a step in the 3-hydroxypropanoate/4-hydroxybutanoate cycle, an autotrophic CO₂ fixation pathway found in some thermoacidophilic archaea [1]. The enzyme from Sulfolobus tokodaii does not act on either NADH or crotonyl-CoA [2]. Different from EC 1.3.1.8, which acts only on enoyl-CoA derivatives of carbon chain length 4 to 16. Contains Zn²⁺.

Links to other databases:

References:

1.	Berg, I.A., Kockelkorn, D., Buckel, W. and Fuchs, G. A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea. Science 318 (2007) 1782–1786. [DOI] [PMID: 18079405]
2.	Teufel, R., Kung, J.W., Kockelkorn, D., Alber, B.E. and Fuchs, G. 3-hydroxypropionyl-coenzyme A dehydratase and acryloyl-coenzyme A reductase, enzymes of the autotrophic 3-hydroxypropionate/4-hydroxybutyrate cycle in the Sulfolobales. J. Bacteriol. 191 (2009) 4572–4581. [DOI] [PMID: 19429610]

[EC 1.3.1.84 created 2009, modified 2014]

*EC

1.7.3.1

Accepted name:

nitroalkane oxidase

Reaction:

a nitroalkane + H₂O + O₂ = an aldehyde or ketone + nitrite + H₂O₂

Other name(s):

nitroethane oxidase; NAO; nitroethane:oxygen oxidoreductase

Systematic name:

nitroalkane:oxygen oxidoreductase

Comments:

Has an absolute requirement for FAD [4]. While nitroethane may be the physiological substrate [2], the enzyme also acts on several other nitroalkanes, including 1-nitropropane, 2-nitropropane, 1-nitrobutane, 1-nitropentane, 1-nitrohexane, nitrocyclohexane and some nitroalkanols [4]. Differs from EC 1.13.12.16, nitronate monooxygenase, in that the preferred substrates are neutral nitroalkanes rather than anionic nitronates [4].

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 9029-36-1, 65802-82-6

References:

1.	Little, H.N. Oxidation of nitroethane by extracts from Neurospora. J. Biol. Chem. 193 (1951) 347–358. [PMID: 14907722]
2.	Kido, T., Hashizume, K. and Soda, K. Purification and properties of nitroalkane oxidase from Fusarium oxysporum. J. Bacteriol. 133 (1978) 53–58. [PMID: 22538]
3.	Daubner, S.C., Gadda, G., Valley, M.P. and Fitzpatrick, P.F. Cloning of nitroalkane oxidase from Fusarium oxysporum identifies a new member of the acyl-CoA dehydrogenase superfamily. Proc. Natl. Acad. Sci. USA 99 (2002) 2702–2707. [DOI] [PMID: 11867731]
4.	Fitzpatrick, P.F., Orville, A.M., Nagpal, A. and Valley, M.P. Nitroalkane oxidase, a carbanion-forming flavoprotein homologous to acyl-CoA dehydrogenase. Arch. Biochem. Biophys. 433 (2005) 157–165. [DOI] [PMID: 15581574]
5.	Valley, M.P., Tichy, S.E. and Fitzpatrick, P.F. Establishing the kinetic competency of the cationic imine intermediate in nitroalkane oxidase. J. Am. Chem. Soc. 127 (2005) 2062–2066. [DOI] [PMID: 15713081]

[EC 1.7.3.1 created 1961, modified 2006, modified 2009]

1.13.11.32

Transferred entry:

2-nitropropane dioxygenase. Now EC 1.13.12.16, nitronate monooxygenase

[EC 1.13.11.32 created 1984, modified 2006, deleted 2009]

1.13.12.16

Accepted name:

nitronate monooxygenase

Reaction:

ethylnitronate + O₂ = acetaldehyde + nitrite + other products

Other name(s):

NMO; 2-nitropropane dioxygenase (incorrect)

Systematic name:

nitronate:oxygen 2-oxidoreductase (nitrite-forming)

Comments:

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

Links to other databases:

References:

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

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

1.14.14.7

Transferred entry:

tryptophan 7-halogenase. As oxygen is completely reduced to H₂O and is not incorporated into the donor chloride, the enzyme has been transferred to EC 1.14.19.9, tryptophan 7-halogenase

[EC 1.14.14.7 created 2009, deleted 2014]

2.1.1.163

Accepted name:

demethylmenaquinone methyltransferase

Reaction:

a demethylmenaquinol + S-adenosyl-L-methionine = a menaquinol + S-adenosyl-L-homocysteine

For diagram of vitamin-K biosynthesis, click here

Other name(s):

S-adenosyl-L-methione—DMK methyltransferase; demethylmenaquinone C-methylase; 2-heptaprenyl-1,4-naphthoquinone methyltransferase; 2-demethylmenaquinone methyltransferase; S-adenosyl-L-methione:2-demethylmenaquinone methyltransferase

Systematic name:

S-adenosyl-L-methione:demethylmenaquinone methyltransferase

Comments:

The enzyme catalyses the last step in menaquinone biosynthesis. It is able to accept substrates with varying polyprenyl side chain length (the chain length is determined by polyprenyl diphosphate synthase)[1]. The enzyme from Escherichia coli also catalyses the conversion of 2-methoxy-6-octaprenyl-1,4-benzoquinone to 5-methoxy-2-methyl-3-octaprenyl-1,4-benzoquinone during the biosynthesis of ubiquinone [4]. The enzyme probably acts on menaquinol rather than menaquinone.

Links to other databases:

References:

1.	Koike-Takeshita, A., Koyama, T. and Ogura, K. Identification of a novel gene cluster participating in menaquinone (vitamin K₂) biosynthesis. Cloning and sequence determination of the 2-heptaprenyl-1,4-naphthoquinone methyltransferase gene of Bacillus stearothermophilus. J. Biol. Chem. 272 (1997) 12380–12383. [DOI] [PMID: 9139683]
2.	Wissenbach, U., Ternes, D. and Unden, G. An Escherichia coli mutant containing only demethylmenaquinone, but no menaquinone: effects on fumarate, dimethylsulfoxide, trimethylamine N-oxide and nitrate respiration. Arch. Microbiol. 158 (1992) 68–73. [PMID: 1444716]
3.	Catala, F., Azerad, R. and Lederer, E. Sur les propriétés de la desméthylménaquinone C-méthylase de Mycobacterium phlei. Int. Z. Vitaminforsch. 40 (1970) 363–373. [PMID: 5450997]
4.	Lee, P.T., Hsu, A.Y., Ha, H.T. and Clarke, C.F. A C-methyltransferase involved in both ubiquinone and menaquinone biosynthesis: isolation and identification of the Escherichia coli ubiE gene. J. Bacteriol. 179 (1997) 1748–1754. [DOI] [PMID: 9045837]

[EC 2.1.1.163 created 2009]

2.3.1.188

Accepted name:

ω-hydroxypalmitate O-feruloyl transferase

Reaction:

feruloyl-CoA + 16-hydroxypalmitate = CoA + 16-feruloyloxypalmitate

Other name(s):

hydroxycinnamoyl-CoA ω-hydroxypalmitic acid O-hydroxycinnamoyltransferase; HHT

Systematic name:

feruloyl-CoA:16-hydroxypalmitate feruloyltransferase

Comments:

p-Coumaroyl-CoA and sinapoyl-CoA also act as substrates. The enzyme is widely distributed in roots of higher plants.

Links to other databases:

References:

1.	Lotfy, S., Negrel, J. and Javelle, F. Formation of feruloyloxypalmitic acid by an enzyme from wound-healing potato tuber discs. Phytochemistry 35 (1994) 1419–1424.
2.	Lotfy, S. Javelle, F. and Negrel, J. Distribution of hydroxycinnamoyl-CoA ω-hydroxypalmitic acid O-hydroxycinnamoyltransferase in higher plants. Phytochemistry 40 (1995) 389–391.
3.	Lotfy, S. Javelle, F. and Negrel, J. Purification and characterization of hydroxycinnamoyl-CoA ω-hydroxypalmitic acid O-hydroxycinnamoyltransferase from tobacco (Nicotiana tabacum L.) cell-suspension cultures. Planta 199 (1996) 475–480.

[EC 2.3.1.188 created 2009]

2.4.1.247

Accepted name:

β-D-galactosyl-(1→4)-L-rhamnose phosphorylase

Reaction:

β-D-galactosyl-(1→4)-L-rhamnose + phosphate = L-rhamnose + α-D-galactose 1-phosphate

Other name(s):

D-galactosyl-β1→4-L-rhamnose phosphorylase; GalRhaP

Systematic name:

β-D-galactosyl-(1→4)-L-rhamnose:phosphate 1-α-D-galactosyltransferase

Comments:

The enzyme from Clostridium phytofermentans is also active towards towards β-D-galactosyl derivatives of L-mannose, L-lyxose, D-glucose, 2-deoxy-D-glucose, and D-galactose in this order. Differs from 1,3-β-galactosyl-N-acetylhexosamine phosphorylase (EC 2.4.1.211) in being active towards L-rhamnose and inactive towards N-acetyl hexosamine derivatives.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 1236189-79-9

References:

1.	Nakajima, M., Nishimoto, M. and Kitaoka, M. Characterization of three β-galactoside phosphorylases from Clostridium phytofermentans: discovery of D-galactosyl-β1→4-L-rhamnose phosphorylase. J. Biol. Chem. 284 (2009) 19220–19227. [DOI] [PMID: 19491100]

[EC 2.4.1.247 created 2009]

2.4.1.248

Accepted name:

cycloisomaltooligosaccharide glucanotransferase

Reaction:

cyclizes part of a (1→6)-α-D-glucan chain by formation of a (1→6)-α-D-glucosidic bond

Systematic name:

(1→6)-α-D-glucan:(1→6)-α-D-glucan 6-α-D-[1→6α-D-glucano]-transferase (cyclizing)

Comments:

Specific for (1→6)-α-D-glucans (dextrans) and, unlike cyclomaltodextrin glucanotransferase (EC 2.4.1.19), without activity towards (1→4)-α-D-glucans, such as amylose. It also has no activity on oligosaccharides, such as amylopectin and pullulan, containing (1→6)-α-D-glucosidic linkages at branch points. The enzyme from Bacillus circulans T-3040 has been shown to form cycloisomalto-oligosaccharides of three sizes (7, 8 and 9 glucose units). It will also catalyse the disproportionation of two isomalto-oligosaccharides molecules to yield a series of isomalto-oligosachharides and the addition of D-glucose to cycloisomalto-oligosaccharides with ring opening to form isomalto-oligosaccharides.

Links to other databases:

References:

1.	Oguma T, Horiuchi, T, and Kobayashi M. Novel Cyclic dextrins, Cycloisomaltooligosaccharides, from Bacillus sp. T-3040 culture. Biosci. Biotech. Biochem. 57 (1993) 1225–1227.
2.	Oguma, T., Tobe, K. and Kobayashi, M. Purification and properties of a novel enzyme from Bacillus spp. T-3040, which catalyzes the conversion of dextran to cyclic isomaltooligosaccharides. FEBS Lett. 345 (1994) 135–138. [DOI] [PMID: 7515357]
3.	Yamamoto, T., Terasawa, K., Kim, Y.M., Kimura, A., Kitamura, Y., Kobayashi, M. and Funane, K. Identification of catalytic amino acids of cyclodextran glucanotransferase from Bacillus circulans T-3040. Biosci. Biotechnol. Biochem. 70 (2006) 1947–1953. [DOI] [PMID: 16926507]

[EC 2.4.1.248 created 2009]

2.4.1.249

Accepted name:

delphinidin 3′,5′-O-glucosyltransferase

Reaction:

2 UDP-glucose + delphinidin 3-O-(6′′-O-malonyl)-β-D-glucoside = 2 UDP + delphinidin 3-O-(6′′-O-malonyl)-β-D-glucoside-3′,5′-di-O-β-D-glucoside (overall reaction)
(1a) UDP-glucose + delphinidin 3-O-(6′′-O-malonyl)-β-D-glucoside = UDP + delphinidin 3-O-(6′′-O-malonyl)-β-D-glucoside-3′-O-β-D-glucoside
(1b) UDP-glucose + delphinidin 3-O-(6′′-O-malonyl)-β-D-glucoside-3′-O-β-D-glucoside = UDP + delphinidin 3-O-(6′′-O-malonyl)-β-D-glucoside-3′,5′-di-O-β-D-glucoside

For diagram of anthocyanidin acylglucoside biosynthesis, click here

Glossary:

delphinidin 3-O-(6′′-O-malonyl)-β-D-glucoside-3′,5′-di-O-β-D-glucoside = ternatin C5

Other name(s):

UDP-glucose:anthocyanin 3′,5′-O-glucosyltransferase; UA3′5’GZ

Systematic name:

UDP-glucose:delphinidin 3-O-(6′′-O-malonyl)-β-D-glucoside 3′-O-glucosyltransferase

Comments:

Ternatins are a group of polyacetylated delphinidin glucosides that confer blue color to the petals of Clitoria ternatea (butterfly pea). This enzyme catalyses two reactions in the biosynthesis of ternatin C5: the conversion of delphinidin 3-O-(6′′-O-malonyl)-β-D-glucoside to delphinidin 3-O-(6′′-O-malonyl)-β-D-glucoside-3′-O-β-D-glucoside, followed by the conversion of the later to ternatin C5, by transferring two glucosyl groups in a stepwise manner [1].

Links to other databases:

References:

1.	Kogawa, K., Kato, N., Kazuma, K., Noda, N. and Suzuki, M. Purification and characterization of UDP-glucose: anthocyanin 3′,5′-O-glucosyltransferase from Clitoria ternatea. Planta 226 (2007) 1501–1509. [DOI] [PMID: 17668234]

[EC 2.4.1.249 created 2009]

2.4.2.41

Accepted name:

xylogalacturonan β-1,3-xylosyltransferase

Reaction:

Transfers a xylosyl residue from UDP-D-xylose to a D-galactose residue in xylogalacturonan, forming a β-1,3-D-xylosyl-D-galactose linkage.

Other name(s):

xylogalacturonan xylosyltransferase; XGA xylosyltransferase

Systematic name:

UDP-D-xylose:xylogalacturonan 3-β-D-xylosyltransferase

Comments:

Involved in plant cell wall synthesis. The enzyme from Arabidopsis thaliana also transfers D-xylose from UDP-D-xylose onto oligogalacturonide acceptors. The enzyme did not show significant activity with UDP-glucose, UDP-galactose, or UDP-N-acetyl-D-glucosamine as sugar donors.

Links to other databases:

References:

Jensen, J.K., Sorensen, S.O., Harholt, J., Geshi, N., Sakuragi, Y., Moller, I., Zandleven, J., Bernal, A.J., Jensen, N.B., Sorensen, C., Pauly, M., Beldman, G., Willats, W.G. and Scheller, H.V. Identification of a xylogalacturonan xylosyltransferase involved in pectin biosynthesis in Arabidopsis. Plant Cell 20 (2008) 1289–1302. [DOI] [PMID: 18460606]

[EC 2.4.2.41 created 2009]

2.5.1.8

Transferred entry:

tRNA isopentenyltransferase. As it is now known that the substrate is dimethylallyl diphosphate, the enzyme has been transferred to EC 2.5.1.75, tRNA dimethylallyltransferase

[EC 2.5.1.8 created 1972, deleted 2009]

2.5.1.73

Accepted name:

O-phospho-L-seryl-tRNA:Cys-tRNA synthase

Reaction:

O-phospho-L-seryl-tRNA^Cys + sulfide = L-cysteinyl-tRNA^Cys + phosphate

Other name(s):

SepCysS; Sep-tRNA:Cys-tRNA synthase

Systematic name:

O-phospho-L-seryl-tRNA^Cys:hydrogen sulfide 2-aminopropanoate transferase

Comments:

In organisms like Archaeoglobus fulgidus lacking EC 6.1.1.16 (cysteine—tRNA ligase) for the direct Cys-tRNA^Cys formation, Cys-tRNA^Cys is produced by an indirect pathway, in which EC 6.1.1.27 (O-phosphoseryl-tRNA ligase) ligates O-phosphoserine to tRNA^Cys, and EC 2.5.1.73 converts the produced O-phospho-L-seryl-tRNA^Cys to Cys-tRNA^Cys. The SepRS/SepCysS pathway is the sole route for cysteine biosynthesis in the organism [1]. Methanosarcina mazei can use both pathways, the direct route using EC 6.1.1.16 (cysteine—tRNA ligase) and the indirect pathway with EC 6.1.1.27 (O-phosphoseryl-tRNA ligase) and EC 2.5.1.73 [2].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 1239229-21-0

References:

1.	Fukunaga, R. and Yokoyama, S. Structural insights into the second step of RNA-dependent cysteine biosynthesis in archaea: crystal structure of Sep-tRNA:Cys-tRNA synthase from Archaeoglobus fulgidus. J. Mol. Biol. 370 (2007) 128–141. [DOI] [PMID: 17512006]
2.	Hauenstein, S.I. and Perona, J.J. Redundant synthesis of cysteinyl-tRNA^Cys in Methanosarcina mazei. J. Biol. Chem. 283 (2008) 22007–22017. [DOI] [PMID: 18559341]
3.	Yuan, J., Palioura, S., Salazar, J.C., Su, D., O'Donoghue, P., Hohn, M.J., Cardoso, A.M., Whitman, W.B. and Soll, D. RNA-dependent conversion of phosphoserine forms selenocysteine in eukaryotes and archaea. Proc. Natl. Acad. Sci. USA 103 (2006) 18923–18927. [DOI] [PMID: 17142313]

[EC 2.5.1.73 created 2009]

2.5.1.74

Accepted name:

1,4-dihydroxy-2-naphthoate polyprenyltransferase

Reaction:

an all-trans-polyprenyl diphosphate + 1,4-dihydroxy-2-naphthoate = a demethylmenaquinone + diphosphate + CO₂

For diagram of vitamin K biosynthesis, click here

Glossary:

menaquinone = vitamin K₂

Systematic name:

all-trans-polyprenyl-diphosphate:1,4-dihydroxy-2-naphthoate polyprenyltransferase

Comments:

This enzyme catalyses a step in the synthesis of menaquinone, in which the prenyl chain synthesized by polyprenyl diphosphate synthase is transferred to 1,4-dihydroxy-2-naphthoate (DHNA). The bacterial enzyme is an inner membrane protein [1], with the C-terminus located in the periplasm [3]. It is highly specific for DHNA but not for a specific length of the prenyl chain [2].

Links to other databases:

References:

1.	Shineberg, B. and Young, I.G. Biosynthesis of bacterial menaquinones: the membrane-associated 1,4-dihydroxy-2-naphthoate octaprenyltransferase of Escherichia coli. Biochemistry 15 (1976) 2754–2758. [PMID: 949474]
2.	Saito, Y. and Ogura, K. Biosynthesis of menaquinones. Enzymatic prenylation of 1,4-dihydroxy-2-naphthoate by Micrococcus luteus membrane fractions. J. Biochem. 89 (1981) 1445–1452. [PMID: 7275947]
3.	Suvarna, K., Stevenson, D., Meganathan, R. and Hudspeth, M.E. Menaquinone (vitamin K₂) biosynthesis: localization and characterization of the menA gene from Escherichia coli. J. Bacteriol. 180 (1998) 2782–2787. [PMID: 9573170]
4.	Daley, D.O., Rapp, M., Granseth, E., Melen, K., Drew, D. and von Heijne, G. Global topology analysis of the Escherichia coli inner membrane proteome. Science 308 (2005) 1321–1323. [DOI] [PMID: 15919996]

[EC 2.5.1.74 created 2009]

2.5.1.75

Accepted name:

tRNA dimethylallyltransferase

Reaction:

prenyl diphosphate + adenosine³⁷ in tRNA = diphosphate + N⁶-(3-methylbut-2-en-1-yl)-adenosine³⁷ in tRNA

For diagram of N⁶-(Dimethylallyl)adenosine³⁷ modified tRNA biosynthesis, click here

Glossary:

N⁶-(3-methylbut-2-en-1-yl)-adenine³⁷ in tRNA = N⁶-dimethylallyladenine³⁷ in tRNA

Other name(s):

tRNA prenyltransferase; MiaA; transfer ribonucleate isopentenyltransferase (incorrect); Δ²-isopentenyl pyrophosphate:tRNA-Δ²-isopentenyl transferase (incorrect); Δ²-isopentenyl pyrophosphate:transfer ribonucleic acid Δ²-isopentenyltransferase (incorrect); dimethylallyl-diphosphate: tRNA dimethylallyltransferase; dimethylallyl-diphosphate:adenine³⁷ in tRNA dimethylallyltransferase

Systematic name:

prenyl-diphosphate:adenine³⁷ in tRNA prenyltransferase

Comments:

Formerly known as tRNA isopentenyltransferase, but it is now known that prenyl diphosphate, rather than isopentenyl diphosphate, is the substrate.

Links to other databases:

References:

1.	Leung, H.C., Chen, Y. and Winkler, M.E. Regulation of substrate recognition by the MiaA tRNA prenyltransferase modification enzyme of Escherichia coli K-12. J. Biol. Chem. 272 (1997) 13073–13083. [DOI] [PMID: 9148919]
2.	Soderberg, T. and Poulter, C.D. Escherichia coli dimethylallyl diphosphate:tRNA dimethylallyltransferase: essential elements for recognition of tRNA substrates within the anticodon stem-loop. Biochemistry 39 (2000) 6546–6553. [DOI] [PMID: 10828971]
3.	Moore, J.A., Mathis, J.R. and Poulter, C.D. Escherichia coli dimethylallyl diphosphate:tRNA dimethylallyltransferase: pre-steady-state kinetic studies. Biochim. Biophys. Acta 1479 (2000) 166–174. [DOI] [PMID: 11004538]

[EC 2.5.1.75 created 1972 as EC 2.5.1.8, transferred 2009 to EC 2.5.1.75]

2.5.1.76

Accepted name:

cysteate synthase

Reaction:

O-phospho-L-serine + sulfite = L-cysteate + phosphate

Other name(s):

sulfite:O-phospho-L-serine sulfotransferase (phosphate-hydrolysing, L-cysteate-forming)

Systematic name:

sulfite:O-phospho-L-serine sulfonotransferase (phosphate-hydrolysing, L-cysteate-forming)

Comments:

A pyridoxal-phosphate protein. It is highly specific for O-phospho-L-serine and sulfite. The reaction proceeds through a dehydroalanine (2-aminoacrylic acid) intermediate. The enzyme from Methanosarcina acetivorans is evolutionarily related to threonine synthase (EC 4.2.3.1), but the reaction is more similar to that of O-phosphoserine sulfhydrylase (EC 2.5.1.65).

Links to other databases:

References:

1.	Graham, D.E., Taylor, S.M., Wolf, R.Z. and Namboori, S.C. Convergent evolution of coenzyme M biosynthesis in the Methanosarcinales: cysteate synthase evolved from an ancestral threonine synthase. Biochem. J. 424 (2009) 467–478. [DOI] [PMID: 19761441]

[EC 2.5.1.76 created 2009]

*EC

2.7.1.119

Accepted name:

hygromycin-B 7′′-O-kinase

Reaction:

ATP + hygromycin B = ADP + 7′′-O-phosphohygromycin B

For diagram click here

Other name(s):

hygromycin B phosphotransferase; hygromycin-B kinase (ambiguous)

Systematic name:

ATP:hygromycin-B 7′′-O-phosphotransferase

Comments:

Phosphorylates the antibiotics hygromycin B, 1-N-hygromycin B and destomycin, but not hygromycin B2, at the 7′′-hydroxy group in the destomic acid ring.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 88361-67-5

References:

1.	Zalacain, M., Pardo, J.M. and Jiménez, A. Purification and characterization of a hygromycin B phosphotransferase from Streptomyces hygroscopicus. Eur. J. Biochem. 162 (1987) 419–422. [DOI] [PMID: 3026811]

[EC 2.7.1.119 created 1989, modified 2009, modified 2011]

2.7.1.163

Accepted name:

hygromycin B 4-O-kinase

Reaction:

ATP + hygromycin B = ADP + 4-O-phosphohygromycin B

Other name(s):

hygromycin-B kinase (ambiguous)

Systematic name:

ATP:hygromycin-B 4-O-phosphotransferase

Comments:

Phosphorylates the antibiotic hygromycin B. Whereas the enzyme from Streptomyces hygroscopicus (EC 2.7.1.119; hygromycin-B 7′′-O-kinase) catalyses the formation of 7′′-O-phosphohygromycin B, this enzyme, found in Escherichia coli carrying a plasmid conferring resistance to hygromycin-B, forms 4-O-phosphohygromycin B.

Links to other databases:

References:

1.	Rao, R.N., Allen, N.E., Hobbs, J.N., Jr., Alborn, W.E., Jr., Kirst, H.A. and Paschal, J.W. Genetic and enzymatic basis of hygromycin B resistance in Escherichia coli. Antimicrob. Agents Chemother. 24 (1983) 689–695. [PMID: 6318654]

[EC 2.7.1.163 created 2009]

2.7.1.164

Accepted name:

O-phosphoseryl-tRNA^Sec kinase

Reaction:

ATP + L-seryl-tRNA^Sec = ADP + O-phospho-L-seryl-tRNA^Sec

Other name(s):

PSTK; phosphoseryl-tRNA[Ser]Sec kinase; phosphoseryl-tRNA^Sec kinase

Systematic name:

ATP:L-seryl-tRNA^Sec O-phosphotransferase

Comments:

In archaea and eukarya selenocysteine formation is achieved by a two-step process: O-phosphoseryl-tRNA^Sec kinase (PSTK) phosphorylates the endogenous L-seryl-tRNA^Sec to O-phospho-L-seryl-tRNA^Sec, and then this misacylated amino acid-tRNA species is converted to L-selenocysteinyl-tRNA^Sec by EC 2.9.1.2 (Sep-tRNA:Sec-tRNA synthase).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 91273-83-5

References:

1.	Carlson, B.A., Xu, X.M., Kryukov, G.V., Rao, M., Berry, M.J., Gladyshev, V.N. and Hatfield, D.L. Identification and characterization of phosphoseryl-tRNA[Ser]Sec kinase. Proc. Natl. Acad. Sci. USA 101 (2004) 12848–12853. [DOI] [PMID: 15317934]
2.	Sherrer, R.L., O'Donoghue, P. and Soll, D. Characterization and evolutionary history of an archaeal kinase involved in selenocysteinyl-tRNA formation. Nucleic Acids Res. 36 (2008) 1247–1259. [DOI] [PMID: 18174226]
3.	Khangulov, S.V., Gladyshev, V.N., Dismukes, G.C. and Stadtman, T.C. Selenium-containing formate dehydrogenase H from Escherichia coli: a molybdopterin enzyme that catalyzes formate oxidation without oxygen transfer. Biochemistry 37 (1998) 3518–3528. [DOI] [PMID: 9521673]

[EC 2.7.1.164 created 2009]

2.9.1.2

Accepted name:

O-phospho-L-seryl-tRNA^Sec:L-selenocysteinyl-tRNA synthase

Reaction:

O-phospho-L-seryl-tRNA^Sec + selenophosphate + H₂O = L-selenocysteinyl-tRNA^Sec + 2 phosphate

Other name(s):

MMPSepSecS; SepSecS; SLA/LP; O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase; O-phospho-L-seryl-tRNA:L-selenocysteinyl-tRNA synthase

Systematic name:

selenophosphate:O-phospho-L-seryl-tRNA^Sec selenium transferase

Comments:

A pyridoxal-phosphate protein [4]. In archaea and eukarya selenocysteine formation is achieved by a two-step process: EC 2.7.1.164 (O-phosphoseryl-tRNA^Sec kinase) phosphorylates the endogenous L-seryl-tRNA^Sec to O-phospho-L-seryl-tRNA^Sec, and then this misacylated amino acid-tRNA species is converted to L-selenocysteinyl-tRNA^Sec by Sep-tRNA:Sec-tRNA synthase.

Links to other databases:

References:

1.	Palioura, S., Sherrer, R.L., Steitz, T.A., Soll, D. and Simonovic, M. The human SepSecS-tRNA^Sec complex reveals the mechanism of selenocysteine formation. Science 325 (2009) 321–325. [DOI] [PMID: 19608919]
2.	Araiso, Y., Palioura, S., Ishitani, R., Sherrer, R.L., O'Donoghue, P., Yuan, J., Oshikane, H., Domae, N., Defranco, J., Soll, D. and Nureki, O. Structural insights into RNA-dependent eukaryal and archaeal selenocysteine formation. Nucleic Acids Res. 36 (2008) 1187–1199. [DOI] [PMID: 18158303]
3.	Aeby, E., Palioura, S., Pusnik, M., Marazzi, J., Lieberman, A., Ullu, E., Soll, D. and Schneider, A. The canonical pathway for selenocysteine insertion is dispensable in Trypanosomes. Proc. Natl. Acad. Sci. USA 106 (2009) 5088–5092. [DOI] [PMID: 19279205]
4.	Yuan, J., Palioura, S., Salazar, J.C., Su, D., O'Donoghue, P., Hohn, M.J., Cardoso, A.M., Whitman, W.B. and Soll, D. RNA-dependent conversion of phosphoserine forms selenocysteine in eukaryotes and archaea. Proc. Natl. Acad. Sci. USA 103 (2006) 18923–18927. [DOI] [PMID: 17142313]

[EC 2.9.1.2 created 2009, modified 2014]

3.1.26.13

Accepted name:

retroviral ribonuclease H

Reaction:

Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA [1-4]. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction [5]. 2. RNA 5′-end directed cleavage 13-19 nucleotides from the RNA end [6,7]. 3. DNA 3′-end directed cleavage 15-20 nucleotides away from the primer terminus [8-10].

Other name(s):

RT/RNase H; retroviral reverse transcriptase RNaseH (gene name); HIV RNase H

Comments:

Retroviral reverse transcriptase is a multifunctional enzyme responsible for viral replication. To perform this task the enzyme combines two distinct activities. The polymerase domain (EC 2.7.7.49, RNA-directed DNA polymerase) occupies the N-terminal two-thirds of the reverse transcriptase whereas the ribonuclease H domain comprises the C-terminal remaining one-third [13,14]. The RNase H domains of Moloney murine leukemia virus and Human immunodeficiency virus display two metal binding sites [15-17]

Links to other databases:

BRENDA, EXPASY, KEGG, PDB, CAS registry number: 9050-76-4

References:

1.	Schultz, S.J., Zhang, M. and Champoux, J.J. Recognition of internal cleavage sites by retroviral RNases H. J. Mol. Biol. 344 (2004) 635–652. [DOI] [PMID: 15533434]
2.	Sarafianos, S.G., Das, K., Tantillo, C., Clark, A.D., Jr., Ding, J., Whitcomb, J.M., Boyer, P.L., Hughes, S.H. and Arnold, E. Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA. EMBO J. 20 (2001) 1449–1461. [DOI] [PMID: 11250910]
3.	Rausch, J.W., Lener, D., Miller, J.T., Julias, J.G., Hughes, S.H. and Le Grice, S.F. Altering the RNase H primer grip of human immunodeficiency virus reverse transcriptase modifies cleavage specificity. Biochemistry 41 (2002) 4856–4865. [DOI] [PMID: 11939780]
4.	Brehm, J.H., Mellors, J.W. and Sluis-Cremer, N. Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Biochemistry 47 (2008) 14020–14027. [DOI] [PMID: 19067547]
5.	Schultz, S.J., Zhang, M., Kelleher, C.D. and Champoux, J.J. Analysis of plus-strand primer selection, removal, and reutilization by retroviral reverse transcriptases. J. Biol. Chem. 275 (2000) 32299–32309. [DOI] [PMID: 10913435]
6.	DeStefano, J.J., Mallaber, L.M., Fay, P.J. and Bambara, R.A. Determinants of the RNase H cleavage specificity of human immunodeficiency virus reverse transcriptase. Nucleic Acids Res. 21 (1993) 4330–4338. [DOI] [PMID: 7692401]
7.	Kati, W.M., Johnson, K.A., Jerva, L.F. and Anderson, K.S. Mechanism and fidelity of HIV reverse transcriptase. J. Biol. Chem. 267 (1992) 25988–25997. [PMID: 1281479]
8.	Palaniappan, C., Fuentes, G.M., Rodriguez-Rodriguez, L., Fay, P.J. and Bambara, R.A. Helix structure and ends of RNA/DNA hybrids direct the cleavage specificity of HIV-1 reverse transcriptase RNase H. J. Biol. Chem. 271 (1996) 2063–2070. [DOI] [PMID: 8567660]
9.	Fu, T.B. and Taylor, J. When retroviral reverse transcriptases reach the end of their RNA templates. J. Virol. 66 (1992) 4271–4278. [PMID: 1376369]
10.	Beilhartz, G.L., Wendeler, M., Baichoo, N., Rausch, J., Le Grice, S. and Gotte, M. HIV-1 reverse transcriptase can simultaneously engage its DNA/RNA substrate at both DNA polymerase and RNase H active sites: implications for RNase H inhibition. J. Mol. Biol. 388 (2009) 462–474. [DOI] [PMID: 19289131]
11.	Huang, H., Chopra, R., Verdine, G.L. and Harrison, S.C. Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science 282 (1998) 1669–1675. [DOI] [PMID: 9831551]
12.	Krug, M.S. and Berger, S.L. Ribonuclease H activities associated with viral reverse transcriptases are endonucleases. Proc. Natl. Acad. Sci. USA 86 (1989) 3539–3543. [DOI] [PMID: 2471188]
13.	Champoux, J.J. and Schultz, S.J. Ribonuclease H: properties, substrate specificity and roles in retroviral reverse transcription. FEBS J. 276 (2009) 1506–1516. [DOI] [PMID: 19228195]
14.	Schultz, S.J. and Champoux, J.J. RNase H activity: structure, specificity, and function in reverse transcription. Virus Res. 134 (2008) 86–103. [DOI] [PMID: 18261820]
15.	Goedken, E.R. and Marqusee, S. Metal binding and activation of the ribonuclease H domain from moloney murine leukemia virus. Protein Eng. 12 (1999) 975–980. [DOI] [PMID: 10585503]
16.	Davies, J.F., 2nd, Hostomska, Z., Hostomsky, Z., Jordan, S.R. and Matthews, D.A. Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase. Science 252 (1991) 88–95. [DOI] [PMID: 1707186]
17.	Pari, K., Mueller, G.A., DeRose, E.F., Kirby, T.W. and London, R.E. Solution structure of the RNase H domain of the HIV-1 reverse transcriptase in the presence of magnesium. Biochemistry 42 (2003) 639–650. [DOI] [PMID: 12534276]

[EC 3.1.26.13 created 2009]

3.2.2.27

Accepted name:

uracil-DNA glycosylase

Reaction:

Hydrolyses single-stranded DNA or mismatched double-stranded DNA and polynucleotides, releasing free uracil

Other name(s):

UdgB (ambiguous); uracil-DNA N-glycosylase; UDG (ambiguous); uracil DNA glycohydrolase

Systematic name:

uracil-DNA deoxyribohydrolase (uracil-releasing)

Comments:

Uracil-DNA glycosylases are widespread enzymes that are found in all living organisms. EC 3.2.2.27 and double-stranded uracil-DNA glycosylase (EC 3.2.2.28) form a central part of the DNA-repair machinery since they initiate the DNA base-excision repair pathway by hydrolysing the N-glycosidic bond between uracil and the deoxyribose sugar thereby catalysing the removal of mis-incorporated uracil from DNA.

Links to other databases:

References:

1.	Lee, M.S., Kim, G.A., Seo, M.S., Lee, J.H. and Kwon, S.T. Characterization of heat-labile uracil-DNA glycosylase from Psychrobacter sp. HJ147 and its application to the polymerase chain reaction. Biotechnol. Appl. Biochem. 52 (2009) 167–175. [DOI] [PMID: 18412541]
2.	Kim, G.A., Lee, M.S., Sun, Y., Lee, B.D., Lee, J.I., Lee, J.H. and Kwon, S.T. Characterization of cold-active uracil-DNA glycosylase from Bacillus sp. HJ171 and its use for contamination control in PCR. Appl. Microbiol. Biotechnol. 80 (2008) 785–794. [DOI] [PMID: 18626641]
3.	Parikh, S.S., Putnam, C.D. and Tainer, J.A. Lessons learned from structural results on uracil-DNA glycosylase. Mutat. Res. 460 (2000) 183–199. [DOI] [PMID: 10946228]
4.	Stivers, J.T. and Drohat, A.C. Uracil DNA glycosylase: insights from a master catalyst. Arch. Biochem. Biophys. 396 (2001) 1–9. [DOI] [PMID: 11716455]

[EC 3.2.2.27 created 2009]

3.2.2.28

Accepted name:

double-stranded uracil-DNA glycosylase

Reaction:

Specifically hydrolyses mismatched double-stranded DNA and polynucleotides, releasing free uracil

Other name(s):

Mug; double-strand uracil-DNA glycosylase; Dug; dsUDG; double-stranded DNA specific UDG; dsDNA specific UDG; UdgB (ambiguous); G:T/U mismatch-specific DNA glycosylase; UDG (ambiguous)

Systematic name:

uracil-double-stranded DNA deoxyribohydrolase (uracil-releasing)

Comments:

No activity on DNA containing a T/G mispair or single-stranded DNA containing either a site-specific uracil or 3,N⁴-ethenocytosine residue [2], significant role for double-stranded uracil-DNA glycosylase in mutation avoidance in non-dividing E. coli [3]. Uracil-DNA glycosylases are widespread enzymes that are found in all living organisms. Uracil-DNA glycosylase (EC 3.2.2.27) and EC 3.2.2.28 form a central part of the DNA-repair machinery since they initiate the DNA base-excision repair pathway by hydrolysing the N-glycosidic bond between uracil and the deoxyribose sugar thereby catalysing the removal of mis-incorporated uracil from DNA.

Links to other databases:

References:

1.	Barrett, T.E., Scharer, O.D., Savva, R., Brown, T., Jiricny, J., Verdine, G.L. and Pearl, L.H. Crystal structure of a thwarted mismatch glycosylase DNA repair complex. EMBO J. 18 (1999) 6599–6609. [DOI] [PMID: 10581234]
2.	Sung, J.S. and Mosbaugh, D.W. Escherichia coli double-strand uracil-DNA glycosylase: involvement in uracil-mediated DNA base excision repair and stimulation of activity by endonuclease IV. Biochemistry 39 (2000) 10224–10235. [DOI] [PMID: 10956012]
3.	Mokkapati, S.K., Fernandez de Henestrosa, A.R. and Bhagwat, A.S. Escherichia coli DNA glycosylase Mug: a growth-regulated enzyme required for mutation avoidance in stationary-phase cells. Mol. Microbiol. 41 (2001) 1101–1111. [DOI] [PMID: 11555290]

[EC 3.2.2.28 created 2009]

3.2.2.29

Accepted name:

thymine-DNA glycosylase

Reaction:

Hydrolyses mismatched double-stranded DNA and polynucleotides, releasing free thymine.

Other name(s):

mismatch-specific thymine-DNA glycosylase; mismatch-specific thymine-DNA N-glycosylase; hTDG; hsTDG; TDG; thymine DNA glycosylase; G/T glycosylase; uracil/thymine DNA glycosylase; T:G mismatch-specific thymidine-DNA glycosylase; G:T mismatch-specific thymine DNA-glycosylase

Systematic name:

thymine-DNA deoxyribohydrolase (thymine-releasing)

Comments:

Thymine-DNA glycosylase is part of the DNA-repair machinery. Thymine removal is fastest when it is from a G/T mismatch with a 5′-flanking C/G pair. The glycosylase removes uracil from G/U, C/U, and T/U base pairs faster than it removes thymine from G/T [3].

Links to other databases:

References:

1.	Waters, T.R. and Swann, P.F. Thymine-DNA glycosylase and G to A transition mutations at CpG sites. Mutat. Res. 462 (2000) 137–147. [DOI] [PMID: 10767625]
2.	Neddermann, P. and Jiricny, J. The purification of a mismatch-specific thymine-DNA glycosylase from HeLa cells. J. Biol. Chem. 268 (1993) 21218–21224. [PMID: 8407958]
3.	Waters, T.R. and Swann, P.F. Kinetics of the action of thymine DNA glycosylase. J. Biol. Chem. 273 (1998) 20007–20014. [DOI] [PMID: 9685338]

[EC 3.2.2.29 created 2009]

3.4.17.23

Accepted name:

angiotensin-converting enzyme 2

Reaction:

angiotensin II + H₂O = angiotensin-(1–7) + L-phenylalanine

Other name(s):

ACE-2; ACE2; hACE2; angiotensin converting enzyme 2; angiotensin converting enzyme-2; Tmem27

Comments:

A transmembrane glycoprotein with an extracellular catalytic domain. Angiotensin-converting enzyme 2 functions as a carboxypeptidase, cleaving a single C-terminal residue from a distinct range of substrates [2]. Catalytic efficiency is 400-fold higher with angiotensin II (1–8) as a substrate than with angiotensin I (1–10). Angiotensin-converting enzyme 2 also efficiently hydrolyses des-Arg⁹-bradykinin, but it does not hydrolyse bradykinin [1]. In peptidase family M2.

Links to other databases:

References:

1.	Vickers, C., Hales, P., Kaushik, V., Dick, L., Gavin, J., Tang, J., Godbout, K., Parsons, T., Baronas, E., Hsieh, F., Acton, S., Patane, M., Nichols, A. and Tummino, P. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J. Biol. Chem. 277 (2002) 14838–14843. [DOI] [PMID: 11815627]
2.	Lambert, D.W., Hooper, N.M. and Turner, A.J. Angiotensin-converting enzyme 2 and new insights into the renin-angiotensin system. Biochem. Pharmacol. 75 (2008) 781–786. [DOI] [PMID: 17897633]
3.	Towler, P., Staker, B., Prasad, S.G., Menon, S., Tang, J., Parsons, T., Ryan, D., Fisher, M., Williams, D., Dales, N.A., Patane, M.A. and Pantoliano, M.W. ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. J. Biol. Chem. 279 (2004) 17996–18007. [DOI] [PMID: 14754895]

[EC 3.4.17.23 created 2009]

3.4.22.69

Accepted name:

SARS coronavirus main proteinase

Reaction:

TSAVLQ┼SGFRK-NH₂ and SGVTFQ┼GKFKK the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase are the two most reactive peptide substrates. The enzyme exhibits a strong preference for substrates containing Gln at P1 position and Leu at P2 position.

Other name(s):

3cLpro; 3C-like protease; coronavirus 3C-like protease; Mpro; SARS 3C-like protease; SARS coronavirus 3CL protease; SARS coronavirus main peptidase; SARS coronavirus main protease; SARS-CoV 3CLpro enzyme; SARS-CoV main protease; SARS-CoV Mpro; severe acute respiratory syndrome coronavirus main protease

Comments:

SARS coronavirus main protease is the key enzyme in SARS coronavirus replicase polyprotein processing. In peptidase family C30.

Links to other databases:

BRENDA, EXPASY, KEGG, MEROPS, PDB

References:

1.	Goetz, D.H., Choe, Y., Hansell, E., Chen, Y.T., McDowell, M., Jonsson, C.B., Roush, W.R., McKerrow, J. and Craik, C.S. Substrate specificity profiling and identification of a new class of inhibitor for the major protease of the SARS coronavirus. Biochemistry 46 (2007) 8744–8752. [DOI] [PMID: 17605471]
2.	Fan, K., Wei, P., Feng, Q., Chen, S., Huang, C., Ma, L., Lai, B., Pei, J., Liu, Y., Chen, J. and Lai, L. Biosynthesis, purification, and substrate specificity of severe acute respiratory syndrome coronavirus 3C-like proteinase. J. Biol. Chem. 279 (2004) 1637–1642. [DOI] [PMID: 14561748]
3.	Akaji, K., Konno, H., Onozuka, M., Makino, A., Saito, H. and Nosaka, K. Evaluation of peptide-aldehyde inhibitors using R188I mutant of SARS 3CL protease as a proteolysis-resistant mutant. Bioorg. Med. Chem. 16 (2008) 9400–9408. [DOI] [PMID: 18845442]

[EC 3.4.22.69 created 2009]

3.4.22.70

Accepted name:

sortase A

Reaction:

The enzyme catalyses a cell wall sorting reaction in which a surface protein with a sorting signal containing a LPXTG motif is cleaved between the Thr and Gly residue. The resulting threonine carboxyl end of the protein is covalently attached to a pentaglycine cross-bridge of peptidoglycan.

Other name(s):

SrtA; SrtA protein; SrtA sortase

Comments:

In peptidase family C60.

Links to other databases:

References:

1.	Ton-That, H., Liu, G., Mazmanian, S.K., Faull, K.F. and Schneewind, O. Purification and characterization of sortase, the transpeptidase that cleaves surface proteins of Staphylococcus aureus at the LPXTG motif. Proc. Natl. Acad. Sci. USA 96 (1999) 12424–12429. [DOI] [PMID: 10535938]
2.	Zong, Y., Bice, T.W., Ton-That, H., Schneewind, O. and Narayana, S.V. Crystal structures of Staphylococcus aureus sortase A and its substrate complex. J. Biol. Chem. 279 (2004) 31383–31389. [DOI] [PMID: 15117963]
3.	Race, P.R., Bentley, M.L., Melvin, J.A., Crow, A., Hughes, R.K., Smith, W.D., Sessions, R.B., Kehoe, M.A., McCafferty, D.G. and Banfield, M.J. Crystal structure of Streptococcus pyogenes sortase A: implications for sortase mechanism. J. Biol. Chem. 284 (2009) 6924–6933. [DOI] [PMID: 19129180]

[EC 3.4.22.70 created 2009]

3.4.22.71

Accepted name:

sortase B

Reaction:

The enzyme catalyses a cell wall sorting reaction in which a surface protein with a sorting signal containing a NPXTN motif is cleaved between the Thr and Asn residue. The resulting threonine carboxyl end of the protein is covalently attached to a pentaglycine cross-bridge of peptidoglycan.

Other name(s):

SrtB

Comments:

In peptidase family C60.

Links to other databases:

References:

1.	Zong, Y., Mazmanian, S.K., Schneewind, O. and Narayana, S.V. The structure of sortase B, a cysteine transpeptidase that tethers surface protein to the Staphylococcus aureus cell wall. Structure 12 (2004) 105–112. [DOI] [PMID: 14725770]
2.	Bierne, H., Garandeau, C., Pucciarelli, M.G., Sabet, C., Newton, S., Garcia-del Portillo, F., Cossart, P. and Charbit, A. Sortase B, a new class of sortase in Listeria monocytogenes. J. Bacteriol. 186 (2004) 1972–1982. [DOI] [PMID: 15028680]
3.	Comfort, D. and Clubb, R.T. A comparative genome analysis identifies distinct sorting pathways in gram-positive bacteria. Infect. Immun. 72 (2004) 2710–2722. [PMID: 15102780]

[EC 3.4.22.71 created 2009]

3.4.23.50

Accepted name:

human endogenous retrovirus K endopeptidase

Reaction:

Processing at the authentic HIV-1 PR recognition site and release of the mature p17 matrix and the p24 capsid protein, as a result of the cleavage of the -SQNY┼PIVQ- cleavage site.

Other name(s):

human endogenous retrovirus K10 endopeptidase; endogenous retrovirus HERV-K10 putative protease; human endogenous retrovirus K retropepsin; HERV K10 endopeptidase; HERV K10 retropepsin; HERV-K PR; HERV-K protease; HERV-K113 protease; human endogenous retrovirus K113 protease; human retrovirus K10 retropepsin

Comments:

In peptidase family A2.

Links to other databases:

BRENDA, EXPASY, KEGG, MEROPS, PDB

References:

Towler, E.M., Gulnik, S.V., Bhat, T.N., Xie, D., Gustschina, E., Sumpter, T.R., Robertson, N., Jones, C., Sauter, M., Mueller-Lantzsch, N., Debouck, C. and Erickson, J.W. Functional characterization of the protease of human endogenous retrovirus, K10: can it complement HIV-1 protease. Biochemistry 37 (1998) 17137–17144. [DOI] [PMID: 9860826]

[EC 3.4.23.50 created 2009]

3.4.23.51

Accepted name:

HycI peptidase

Reaction:

This enzyme specifically removes a 32-amino acid peptide from the C-terminus of the precursor of the large subunit of hydrogenase 3 in Escherichia coli by cleavage at the C-terminal side of Arg⁵³⁷.

Other name(s):

HycI; HycE processing protein

Comments:

The reaction requires nickel to be bound to the precursor of the large subunit of hydrogenase 3. The endopeptidase uses the metal in the large subunit of [NiFe]-hydrogenases as a recognition motif [1]. In peptidase family A31.

Links to other databases:

References:

1.	Theodoratou, E., Paschos, A., Magalon, A., Fritsche, E., Huber, R. and Bock, A. Nickel serves as a substrate recognition motif for the endopeptidase involved in hydrogenase maturation. Eur. J. Biochem. 267 (2000) 1995–1999. [DOI] [PMID: 10727938]
2.	Yang, F., Hu, W., Xu, H., Li, C., Xia, B. and Jin, C. Solution structure and backbone dynamics of an endopeptidase HycI from Escherichia coli: implications for mechanism of the [NiFe] hydrogenase maturation. J. Biol. Chem. 282 (2007) 3856–3863. [DOI] [PMID: 17150961]

[EC 3.4.23.51 created 2009]

3.4.24.87

Accepted name:

ADAMTS13 endopeptidase

Reaction:

The enzyme cleaves the von Willebrand factor at bond Tyr⁸⁴²┼Met⁸⁴³ within the A2 domain

Other name(s):

ADAMTS VWF cleaving metalloprotease; ADAMTS-13; ADAMTS13; vWF-cleaving protease; VWF-CP; vWF-degrading protease; Upshaw factor; von Willebrand factor cleaving protease; ADAMTS13 peptidase

Comments:

In peptidase family M12.

Links to other databases:

References:

1.	Fujikawa, K., Suzuki, H., McMullen, B. and Chung, D. Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family. Blood 98 (2001) 1662–1666. [PMID: 11535495]
2.	Dong, J.F., Moake, J.L., Nolasco, L., Bernardo, A., Arceneaux, W., Shrimpton, C.N., Schade, A.J., McIntire, L.V., Fujikawa, K. and Lopez, J.A. ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions. Blood 100 (2002) 4033–4039. [DOI] [PMID: 12393397]

[EC 3.4.24.87 created 2009]

3.4.25.2

Accepted name:

HslU—HslV peptidase

Reaction:

ATP-dependent cleavage of peptide bonds with broad specificity.

Other name(s):

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

Comments:

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

Links to other databases:

References:

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

[EC 3.4.25.2 created 2009, modified 2010]

3.5.1.99

Accepted name:

fatty acid amide hydrolase

Reaction:

(1) anandamide + H₂O = arachidonic acid + ethanolamine
(2) oleamide + H₂O = oleic acid + NH₃

Glossary:

anandamide = (5Z,8Z,11Z,14Z)-N-(2-hydroxyethyl)icosa-5,8,11,14-tetraenamide

Other name(s):

FAAH; oleamide hydrolase; anandamide amidohydrolase

Systematic name:

fatty acylamide amidohydrolase

Comments:

Integral membrane protein, the enzyme is responsible for the catabolism of neuromodulatory fatty acid amides, including anandamide and oleamide, occurs in mammalia.

Links to other databases:

References:

1.	Boger, D.L., Fecik, R.A., Patterson, J.E., Miyauchi, H., Patricelli, M.P. and Cravatt, B.F. Fatty acid amide hydrolase substrate specificity. Bioorg. Med. Chem. Lett. 10 (2000) 2613–2616. [DOI] [PMID: 11128635]
2.	Patricelli, M.P., Lashuel, H.A., Giang, D.K., Kelly, J.W. and Cravatt, B.F. Comparative characterization of a wild type and transmembrane domain-deleted fatty acid amide hydrolase: identification of the transmembrane domain as a site for oligomerization. Biochemistry 37 (1998) 15177–15187. [DOI] [PMID: 9790682]
3.	Patricelli, M.P. and Cravatt, B.F. Characterization and manipulation of the acyl chain selectivity of fatty acid amide hydrolase. Biochemistry 40 (2001) 6107–6115. [DOI] [PMID: 11352748]

[EC 3.5.1.99 created 2009]

3.5.1.100

Accepted name:

(R)-amidase

Reaction:

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

Other name(s):

R-stereospecific amidase; R-amidase

Systematic name:

(R)-piperazine-2-carboxamide amidohydrolase

Comments:

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

Links to other databases:

References:

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

[EC 3.5.1.100 created 2009, modified 2011]

3.5.1.101

Accepted name:

L-proline amide hydrolase

Reaction:

(1) (S)-piperidine-2-carboxamide + H₂O = (S)-piperidine-2-carboxylate + NH₃
(2) L-prolinamide + H₂O = L-proline + NH₃

Glossary:

L-pipecolate = piperidine-2-carboxylate

Other name(s):

S-stereoselective piperazine-2-tert-butylcarboxamide hydrolase; LaaA; L-amino acid amidase

Systematic name:

(S)-piperidine-2-carboxamide amidohydrolase

Links to other databases:

References:

1.	Komeda, H., Harada, H., Washika, S., Sakamoto, T., Ueda, M. and Asano, Y. S-stereoselective piperazine-2-tert-butylcarboxamide hydrolase from Pseudomonas azotoformans IAM 1603 is a novel L-amino acid amidase. Eur. J. Biochem. 271 (2004) 1465–1475. [DOI] [PMID: 15066172]

[EC 3.5.1.101 created 2009]

3.6.4.12

Transferred entry:

DNA helicase. Now EC 5.6.2.3, DNA 5′-3′ helicase and EC 5.6.2.4, DNA 3′-5′ helicase

[EC 3.6.4.12 created 2009, deleted 2021]

3.6.4.13

Transferred entry:

RNA helicase. Now covered by EC 5.6.2.5, RNA 5′-3′ helicase, EC 5.6.2.6, RNA 3′-5′ helicase and EC 5.6.2.7, DEAD-box RNA helicase

[EC 3.6.4.13 created 2009, deleted 2024]

3.7.1.11

Accepted name:

cyclohexane-1,2-dione hydrolase

Reaction:

cyclohexane-1,2-dione + H₂O = 6-oxohexanoate

Other name(s):

cyclohexane-1,2-dione acylhydrolase (decyclizing)

Systematic name:

cyclohexane-1,2-dione acylhydrolase (ring-opening)

Comments:

Highly specific; does not act on cyclohexanone or cyclohexane-1,3-dione as substrate.

Links to other databases:

References:

1.	Harder, J. Anaerobic degradation of cyclohexane-1,2-diol by a new Azoarcus species. Arch. Microbiol. 168 (1997) 199–204.
2.	Fraas, S., Steinbach, A.K., Tabbert, A., Harder, J., Ermler, U., Tittmann, K., Meyer, A. and Kroneck P.M.H. Cyclohexane-1,2-dione hydrolase: A new tool to degrade alicyclic compounds. J. Mol. Catalysis B: Enzymatic 61 (2009) 47–49.

[EC 3.7.1.11 created 2009]

4.1.1.90

Accepted name:

peptidyl-glutamate 4-carboxylase

Reaction:

peptidyl-4-carboxyglutamate + 2,3-epoxyphylloquinone + H₂O = peptidyl-glutamate + CO₂ + O₂ + phylloquinol

For diagram of the vitamin K cycle, click here

Other name(s):

vitamin K-dependent carboxylase; γ-glutamyl carboxylase; peptidyl-glutamate 4-carboxylase (2-methyl-3-phytyl-1,4-naphthoquinone-epoxidizing)

Systematic name:

peptidyl-glutamate 4-carboxylase (2-methyl-3-phytyl-1,4-naphthoquinol-epoxidizing)

Comments:

The enzyme can use various vitamin-K derivatives, including menaquinol, but does not contain iron. The mechanism appears to involve the generation of a strong base by oxygenation of vitamin K. It catalyses the post-translational carboxylation of glutamate residues of several proteins of the blood-clotting system. 9–12 glutamate residues are converted to 4-carboxyglutamate (Gla) in a specific domain of the target protein. The 4-pro-S hydrogen of the glutamate residue is removed [5] and there is an inversion of stereochemistry at this position [6].

Links to other databases:

References:

1.	Dowd, P., Hershline, R., Ham, S.W. and Naganathan, S. Vitamin K and energy transduction: a base strength amplification mechanism. Science 269 (1995) 1684–1691. [DOI] [PMID: 7569894]
2.	Furie, B., Bouchard, B.A. and Furie, B.C. Vitamin K-dependent biosynthesis of γ-carboxyglutamic acid. Blood 93 (1999) 1798–1808. [PMID: 10068650]
3.	Rishavy, M.A., Hallgren, K.W., Yakubenko, A.V., Shtofman, R.L., Runge, K.W. and Berkner, K.L. Bronsted analysis reveals Lys²¹⁸ as the carboxylase active site base that deprotonates vitamin K hydroquinone to initiate vitamin K-dependent protein carboxylation. Biochemistry 45 (2006) 13239–13248. [DOI] [PMID: 17073445]
4.	Silva, P.J. and Ramos, M.J. Reaction mechanism of the vitamin K-dependent glutamate carboxylase: a computational study. J. Phys. Chem. B 111 (2007) 12883–12887. [DOI] [PMID: 17935315]
5.	Decottignies-Le Maréchal, P., Ducrocq, C., Marquet, A. and Azerad, R. The stereochemistry of hydrogen abstraction in vitamin K-dependent carboxylation. J. Biol. Chem. 259 (1984) 15010–15012. [PMID: 6150930]
6.	Dubois, J., Dugave, C., Foures, C., Kaminsky, M., Tabet, J.C., Bory, S., Gaudry, M. and Marquet, A. Vitamin K dependent carboxylation: determination of the stereochemical course using 4-fluoroglutamyl-containing substrate. Biochemistry 30 (1991) 10506–10512. [PMID: 1931973]
7.	Rishavy, M.A. and Berkner, K.L. Vitamin K oxygenation, glutamate carboxylation, and processivity: defining the three critical facets of catalysis by the vitamin K-dependent carboxylase. Adv Nutr 3 (2012) 135–148. [DOI] [PMID: 22516721]

[EC 4.1.1.90 created 2009, modified 2011]

4.1.99.13

Accepted name:

(6-4)DNA photolyase

Reaction:

(6-4) photoproduct (in DNA) = 2 pyrimidine residues (in DNA)

For diagram click here

Other name(s):

DNA photolyase; H64PRH; NF-10; phr (6-4); PL-(6-4); OtCPF1; (6-4) PHR; At64PHR

Systematic name:

(6-4) photoproduct pyrimidine-lyase

Comments:

A flavoprotein (FAD). The overall repair reaction consists of two distinct steps, one of which is light-independent and the other one light-dependent. In the initial light-independent step, a 6-iminium ion is thought to be generated via proton transfer induced by two histidines highly conserved among the (6-4) photolyases. This intermediate spontaneously rearranges to form an oxetane intermediate by intramolecular nucleophilic attack. In the subsequent light-driven reaction, one electron is believed to be transferred from the fully reduced FAD cofactor (FADH^-) to the oxetane intermediate thus forming a neutral FADH radical and an anionic oxetane radical, which spontaneously fractures. The excess electron is then back-transferred to the flavin radical restoring the fully reduced flavin cofactor and a pair of pyrimidine bases [2].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 37290-70-3

References:

1.	Hitomi, K., DiTacchio, L., Arvai, A.S., Yamamoto, J., Kim, S.T., Todo, T., Tainer, J.A., Iwai, S., Panda, S. and Getzoff, E.D. Functional motifs in the (6-4) photolyase crystal structure make a comparative framework for DNA repair photolyases and clock cryptochromes. Proc. Natl. Acad. Sci. USA 106 (2009) 6962–6967. [DOI] [PMID: 19359474]
2.	Schleicher, E., Hitomi, K., Kay, C.W., Getzoff, E.D., Todo, T. and Weber, S. Electron nuclear double resonance differentiates complementary roles for active site histidines in (6-4) photolyase. J. Biol. Chem. 282 (2007) 4738–4747. [DOI] [PMID: 17164245]

[EC 4.1.99.13 created 2009]

4.1.99.14

Accepted name:

spore photoproduct lyase

Reaction:

(5R)-5,6-dihydro-5-(thymidin-7-yl)thymidine (in double-helical DNA) = thymidylyl-(3′→5′)-thymidylate (in double-helical DNA)

For diagram click here

Other name(s):

SAM; SP lyase; SPL; SplB; SplG

Systematic name:

spore photoproduct pyrimidine-lyase

Comments:

This enzyme is a member of the ’AdoMet radical’ (radical SAM) family. The enzyme binds a [4Fe-4S] cluster. The cluster is coordinated by 3 cysteines and an exchangeable SAM molecule [3]. The 5′-deoxy-adenosine radical formed after electron transfer from the [4Fe-4S] cluster to the S-adenosyl-L-methionine, initiates the repair by abstracting the C-6 hydrogen of the spore photoproduct lesion. During the second part of the repair process the SAM molecule is regenerated [3].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 37290-70-3

References:

1.	Chandor, A., Berteau, O., Douki, T., Gasparutto, D., Sanakis, Y., Ollagnier-de-Choudens, S., Atta, M. and Fontecave, M. Dinucleotide spore photoproduct, a minimal substrate of the DNA repair spore photoproduct lyase enzyme from Bacillus subtilis. J. Biol. Chem. 281 (2006) 26922–26931. [DOI] [PMID: 16829676]
2.	Pieck, J.C., Hennecke, U., Pierik, A.J., Friedel, M.G. and Carell, T. Characterization of a new thermophilic spore photoproduct lyase from Geobacillus stearothermophilus (SplG) with defined lesion containing DNA substrates. J. Biol. Chem. 281 (2006) 36317–36326. [DOI] [PMID: 16968710]
3.	Buis, J.M., Cheek, J., Kalliri, E. and Broderick, J.B. Characterization of an active spore photoproduct lyase, a DNA repair enzyme in the radical S-adenosylmethionine superfamily. J. Biol. Chem. 281 (2006) 25994–26003. [DOI] [PMID: 16829680]
4.	Mantel, C., Chandor, A., Gasparutto, D., Douki, T., Atta, M., Fontecave, M., Bayle, P.-A., Mouesca, J.-M. and Bardet, M. Combined NMR and DFT studies for the absolute configuration elucidation of the spore photoproduct, a UV-induced DNA lesion. J. Am. Chem. Soc. 130 (2008) 16978–16984. [DOI] [PMID: 19012397]
5.	Silver, S.C., Chandra, T., Zilinskas, E., Ghose, S., Broderick, W.E. and Broderick, J.B. Complete stereospecific repair of a synthetic dinucleotide spore photoproduct by spore photoproduct lyase. J. Biol. Inorg. Chem. 15 (2010) 943–955. [DOI] [PMID: 20405152]

[EC 4.1.99.14 created 2009, modified 2010]

4.1.99.15

Deleted entry:

S-specific spore photoproduct lyase. This enzyme was classified on the basis of an incorrect reaction. The activity is covered by EC 4.1.99.14, spore photoproduct lyase

[EC 4.1.99.15 created 2009, deleted 2010]

4.2.1.116

Accepted name:

3-hydroxypropionyl-CoA dehydratase

Reaction:

3-hydroxypropanoyl-CoA = acryloyl-CoA + H₂O

For diagram of the 3-hydroxypropanoate cycle, click here and for diagram of the 3-hydroxypropanoate/4-hydroxybutanoate cycle and dicarboxylate/4-hydroxybutanoate cycle in archaea, click here

Glossary:

acryloyl-CoA = acrylyl-CoA
3-hydroxypropanoyl-CoA = 3-hydroxypropionyl-CoA

Other name(s):

3-hydroxypropionyl-CoA hydro-lyase; 3-hydroxypropanoyl-CoA dehydratase

Systematic name:

3-hydroxypropanoyl-CoA hydro-lyase

Comments:

Catalyses a step in the 3-hydroxypropanoate/4-hydroxybutanoate cycle, an autotrophic CO₂ fixation pathway found in some thermoacidophilic archaea [1]. The enzyme from Metallosphaera sedula acts nearly equally as well on (S)-3-hydroxybutanoyl-CoA but not (R)-3-hydroxybutanoyl-CoA [2].

Links to other databases:

References:

1.	Berg, I.A., Kockelkorn, D., Buckel, W. and Fuchs, G. A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea. Science 318 (2007) 1782–1786. [DOI] [PMID: 18079405]
2.	Teufel, R., Kung, J.W., Kockelkorn, D., Alber, B.E. and Fuchs, G. 3-hydroxypropionyl-coenzyme A dehydratase and acryloyl-coenzyme A reductase, enzymes of the autotrophic 3-hydroxypropionate/4-hydroxybutyrate cycle in the Sulfolobales. J. Bacteriol. 191 (2009) 4572–4581. [DOI] [PMID: 19429610]

[EC 4.2.1.116 created 2009]

4.2.1.117

Accepted name:

2-methylcitrate dehydratase (2-methyl-trans-aconitate-forming)

Reaction:

(2S,3S)-2-methylcitrate = 2-methyl-trans-aconitate + H₂O

Glossary:

(2S,3S)-2-methylcitrate = (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate
2-methyl-trans-aconitate = (2E)-but-2-ene-1,2,3-tricarboxylate

Systematic name:

(2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate hydro-lyase (2-methyl-trans-aconitate-forming)

Comments:

Catalyses the dehydration of (2S,3S)-2-methylcitrate, forming the trans isomer of 2-methyl-aconitate (unlike EC 4.2.1.79, which forms only the cis isomer). Part of a propionate degradation pathway. The enzyme from Shewanella oneidensis can also accept citrate and cis-aconitate, but activity with (2S,3S)-2-methylcitrate was approximately 2.5-fold higher. 2-methylisocitrate and isocitrate were not substrates [1]. An iron-sulfur protein.

Links to other databases:

References:

1.	Grimek, T.L. and Escalante-Semerena, J.C. The acnD genes of Shewenella oneidensis and Vibrio cholerae encode a new Fe/S-dependent 2-methylcitrate dehydratase enzyme that requires prpF function in vivo. J. Bacteriol. 186 (2004) 454–462. [DOI] [PMID: 14702315]

[EC 4.2.1.117 created 2009]

4.2.1.118

Accepted name:

3-dehydroshikimate dehydratase

Reaction:

3-dehydro-shikimate = 3,4-dihydroxybenzoate + H₂O

Glossary:

3,4-dihydroxybenzoate = protocatechuate

Systematic name:

3-dehydroshikimate hydro-lyase

Comments:

Catalyses an early step in the biosynthesis of petrobactin, a siderophore produced by many bacteria, including the human pathogen Bacillus anthracis. Requires divalent ions, with a preference for Mn²⁺.

Links to other databases:

References:

1.	Fox, D.T., Hotta, K., Kim, C.Y. and Koppisch, A.T. The missing link in petrobactin biosynthesis: asbF encodes a (-)-3-dehydroshikimate dehydratase. Biochemistry 47 (2008) 12251–12253. [DOI] [PMID: 18975921]
2.	Pfleger, B.F., Kim, Y., Nusca, T.D., Maltseva, N., Lee, J.Y., Rath, C.M., Scaglione, J.B., Janes, B.K., Anderson, E.C., Bergman, N.H., Hanna, P.C., Joachimiak, A. and Sherman, D.H. Structural and functional analysis of AsbF: origin of the stealth 3,4-dihydroxybenzoic acid subunit for petrobactin biosynthesis. Proc. Natl. Acad. Sci. USA 105 (2008) 17133–17138. [DOI] [PMID: 18955706]

[EC 4.2.1.118 created 2009]

4.2.1.119

Accepted name:

enoyl-CoA hydratase 2

Reaction:

(3R)-3-hydroxyacyl-CoA = (2E)-2-enoyl-CoA + H₂O

For diagram of Benzoyl-CoA catabolism, click here

Other name(s):

2-enoyl-CoA hydratase 2; AtECH2; ECH2; MaoC; MFE-2; PhaJAc; D-3-hydroxyacyl-CoA hydro-lyase; D-specific 2-trans-enoyl-CoA hydratase

Systematic name:

(3R)-3-hydroxyacyl-CoA hydro-lyase

Comments:

This enzyme catalyses a hydration step in peroxisomal β-oxidation. The human multifunctional enzyme type 2 (MFE-2) is a 79000 Da enzyme composed of three functional units: (3R)-hydroxyacyl-CoA dehydrogenase, 2-enoyl-CoA hydratase 2 and sterol carrier protein 2-like units [1]. The enzymes from Aeromonas caviae [4] and Arabidopsis thaliana [5] are monofunctional enzymes. 2-Enoyl-CoA hydratase 3 from Candida tropicalis is a part from multifunctional enzyme type 2 [3].

Links to other databases:

References:

1.	Koski, K.M., Haapalainen, A.M., Hiltunen, J.K. and Glumoff, T. Crystal structure of 2-enoyl-CoA hydratase 2 from human peroxisomal multifunctional enzyme type 2. J. Mol. Biol. 345 (2005) 1157–1169. [DOI] [PMID: 15644212]
2.	Fukui, T., Shiomi, N. and Doi, Y. Expression and characterization of (R)-specific enoyl coenzyme A hydratase involved in polyhydroxyalkanoate biosynthesis by Aeromonas caviae. J. Bacteriol. 180 (1998) 667–673. [PMID: 9457873]
3.	Koski, M.K., Haapalainen, A.M., Hiltunen, J.K. and Glumoff, T. Crystallization and preliminary crystallographic data of 2-enoyl-CoA hydratase 2 domain of Candida tropicalis peroxisomal multifunctional enzyme type 2. Acta Crystallogr. D Biol. Crystallogr. 59 (2003) 1302–1305. [PMID: 12832794]
4.	Hisano, T., Fukui, T., Iwata, T. and Doi, Y. Crystallization and preliminary X-ray analysis of (R)-specific enoyl-CoA hydratase from Aeromonas caviae involved in polyhydroxyalkanoate biosynthesis. Acta Crystallogr. D Biol. Crystallogr. 57 (2001) 145–147. [PMID: 11134939]
5.	Goepfert, S., Hiltunen, J.K. and Poirier, Y. Identification and functional characterization of a monofunctional peroxisomal enoyl-CoA hydratase 2 that participates in the degradation of even cis-unsaturated fatty acids in Arabidopsis thaliana. J. Biol. Chem. 281 (2006) 35894–35903. [DOI] [PMID: 16982622]
6.	Engeland, K. and Kindl, H. Evidence for a peroxisomal fatty acid β-oxidation involving D-3-hydroxyacyl-CoAs. Characterization of two forms of hydro-lyase that convert D-(-)-3-hydroxyacyl-CoA into 2-trans-enoyl-CoA. Eur. J. Biochem. 200 (1991) 171–178. [DOI] [PMID: 1879422]

[EC 4.2.1.119 created 2009]

4.2.1.120

Accepted name:

4-hydroxybutanoyl-CoA dehydratase

Reaction:

4-hydroxybutanoyl-CoA = (E)-but-2-enoyl-CoA + H₂O

For diagram of the 3-hydroxypropanoate/4-hydroxybutanoate cycle and dicarboxylate/4-hydroxybutanoate cycle in archaea, click here

Glossary:

4-hydroxybutanoyl-CoA = 4-hydroxybutyryl-CoA
(E)-but-2-enoyl-CoA = crotonyl-CoA

Systematic name:

4-hydroxybutanoyl-CoA hydro-lyase

Comments:

Contains FAD and a [4Fe-4S] iron-sulfur cluster. The enzyme has been characterized from several microorganisms, including Clostridium kluyveri, where it participates in succinate fermentation [1,2], Clostridium aminobutyricum, where it participates in 4-aminobutyrate degradation [3,4], and Metallosphaera sedula, where it participates in the 3-hydroxypropionate/4-hydroxybutyrate cycle, an autotrophic CO₂ fixation pathway found in some thermoacidophilic archaea [5].

Links to other databases:

References:

1.	Bartsch, R.G. and Barker, H.A. A vinylacetyl isomerase from Clostridium kluyveri. Arch. Biochem. Biophys. 92 (1961) 122–132. [DOI] [PMID: 13687513]
2.	Scherf, U., Sohling, B., Gottschalk, G., Linder, D. and Buckel, W. Succinate-ethanol fermentation in Clostridium kluyveri: purification and characterisation of 4-hydroxybutyryl-CoA dehydratase/vinylacetyl-CoA Δ³-Δ²-isomerase. Arch. Microbiol. 161 (1994) 239–245. [PMID: 8161284]
3.	Scherf, U. and Buckel, W. Purification and properties of an iron-sulfur and FAD-containing 4-hydroxybutyryl-CoA dehydratase/vinylacetyl-CoA Δ³-Δ²-isomerase from Clostridium aminobutyricum. Eur. J. Biochem. 215 (1993) 421–429. [DOI] [PMID: 8344309]
4.	Muh, U., Cinkaya, I., Albracht, S.P. and Buckel, W. 4-Hydroxybutyryl-CoA dehydratase from Clostridium aminobutyricum: characterization of FAD and iron-sulfur clusters involved in an overall non-redox reaction. Biochemistry 35 (1996) 11710–11718. [DOI] [PMID: 8794752]
5.	Berg, I.A., Kockelkorn, D., Buckel, W. and Fuchs, G. A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea. Science 318 (2007) 1782–1786. [DOI] [PMID: 18079405]

[EC 4.2.1.120 created 2009]

4.2.3.45

Accepted name:

phyllocladan-16α-ol synthase

Reaction:

(+)-copalyl diphosphate + H₂O = phyllocladan-16α-ol + diphosphate

For diagram of abietadiene, aphidicolanol, sclareol and terpentetriene biosynthesis, click here and for mechanism of reaction, click here

Other name(s):

PaDC1

Systematic name:

(+)-copalyl-diphosphate diphosphate-lyase (phyllocladan-16α-ol-forming)

Comments:

The adjacent gene PaDC2 codes EC 5.5.1.12 copalyl diphosphate synthase.

Links to other databases:

References:

Toyomasu, T., Niida, R., Kenmoku, H., Kanno, Y., Miura, S., Nakano, C., Shiono, Y., Mitsuhashi, W., Toshima, H., Oikawa, H., Hoshino, T., Dairi, T., Kato, N. and Sassa, T. Identification of diterpene biosynthetic gene clusters and functional analysis of labdane-related diterpene cyclases in Phomopsis amygdali. Biosci. Biotechnol. Biochem. 72 (2008) 1038–1047. [DOI] [PMID: 18391465]

[EC 4.2.3.45 created 2009]

4.99.1.8

Accepted name:

heme ligase

Reaction:

2 ferriprotoporphyrin IX = β-hematin

Other name(s):

heme detoxification protein; HDP; hemozoin synthase

Systematic name:

Fe³⁺:ferriprotoporphyrin IX ligase (β-hematin-forming)

Comments:

This heme detoxifying enzyme is found in Plasmodium parasites and converts toxic heme to crystalline hemozoin. These organisms lack the mammalian heme oxygenase for elimination of heme.

Links to other databases:

References:

1.	Jani, D., Nagarkatti, R., Beatty, W., Angel, R., Slebodnick, C., Andersen, J., Kumar, S. and Rathore, D. HDP-a novel heme detoxification protein from the malaria parasite. PLoS Pathog. 4 (2008) e1000053. [DOI] [PMID: 18437218]

[EC 4.99.1.8 created 2009]

6.1.1.27

Accepted name:

O-phospho-L-serine—tRNA ligase

Reaction:

ATP + O-phospho-L-serine + tRNA^Cys = AMP + diphosphate + O-phospho-L-seryl-tRNA^Cys

Other name(s):

O-phosphoseryl-tRNA ligase; non-canonical O-phosphoseryl-tRNA synthetase; SepRS

Systematic name:

O-phospho-L-serine:tRNA^Cys ligase (AMP-forming)

Comments:

In organisms like Archaeoglobus fulgidus lacking EC 6.1.1.16 (cysteine—tRNA ligase) for the direct Cys-tRNA^Cys formation, Cys-tRNA^Cys is produced by an indirect pathway, in which EC 6.1.1.27 (O-phosphoseryl-tRNA ligase) ligates O-phosphoserine to tRNA^Cys, and EC 2.5.1.73 (O-phospho-L-seryl-tRNA: Cys-tRNA synthase) converts the produced O-phospho-L-seryl-tRNA^Cys to Cys-tRNA^Cys. The SepRS/SepCysS pathway is the sole route for cysteine biosynthesis in the organism [1]. Methanosarcina mazei can use both pathways, the direct route using EC 6.1.1.16 (cysteine—tRNA ligase) and the indirect pathway with EC 6.1.1.27 and EC 2.5.1.73 (O-phospho-L-seryl-tRNA: Cys-tRNA synthase) [2].

Links to other databases:

References:

1.	Fukunaga, R. and Yokoyama, S. Structural insights into the first step of RNA-dependent cysteine biosynthesis in archaea. Nat. Struct. Mol. Biol. 14 (2007) 272–279. [DOI] [PMID: 17351629]
2.	Hauenstein, S.I. and Perona, J.J. Redundant synthesis of cysteinyl-tRNA^Cys in Methanosarcina mazei. J. Biol. Chem. 283 (2008) 22007–22017. [DOI] [PMID: 18559341]

[EC 6.1.1.27 created 2009]

6.2.1.36

Accepted name:

3-hydroxypropionyl-CoA synthase

Reaction:

3-hydroxypropanoate + ATP + CoA = 3-hydroxypropanoyl-CoA + AMP + diphosphate

For diagram of the 3-hydroxypropanoate cycle, click here and for diagram of the 3-hydroxypropanoate/4-hydroxybutanoate cycle and dicarboxylate/4-hydroxybutanoate cycle in archaea, click here

Glossary:

3-hydroxypropionyl-CoA = 3-hydroxypropanoyl-CoA

Other name(s):

3-hydroxypropionyl-CoA synthetase (AMP-forming); 3-hydroxypropionate—CoA ligase

Systematic name:

hydroxypropanoate:CoA ligase (AMP-forming)

Comments:

Catalyses a step in the 3-hydroxypropanoate/4-hydroxybutanoate cycle, an autotrophic CO₂ fixation pathway found in some thermoacidophilic archaea [1,2].The enzymes from Metallosphaera sedula and Sulfolobus tokodaii can also use propionate, acrylate, acetate, and butanoate as substrates [2], and are thus different from EC 6.2.1.17 (propionate—CoA ligase), which does not accept acetate or butanoate.

Links to other databases:

References:

1.	Berg, I.A., Kockelkorn, D., Buckel, W. and Fuchs, G. A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea. Science 318 (2007) 1782–1786. [DOI] [PMID: 18079405]
2.	Alber, B.E., Kung, J.W. and Fuchs, G. 3-Hydroxypropionyl-coenzyme A synthetase from Metallosphaera sedula, an enzyme involved in autotrophic CO₂ fixation. J. Bacteriol. 190 (2008) 1383–1389. [DOI] [PMID: 18165310]

[EC 6.2.1.36 created 2009]

6.3.1.13

Accepted name:

L-cysteine:1D-myo-inositol 2-amino-2-deoxy-α-D-glucopyranoside ligase

Reaction:

1-O-(2-amino-2-deoxy-α-D-glucopyranosyl)-1D-myo-inositol + L-cysteine + ATP = 1-O-[2-(L-cysteinamido)-2-deoxy-α-D-glucopyranosyl]-1D-myo-inositol + AMP + diphosphate

For diagram of mycothiol biosynthesis, click here

Glossary:

mycothiol = 1-O-[2-(N²-acetyl-L-cysteinamido)-2-deoxy^--D-glucopyranosyl]-1D-myo-inositol

Other name(s):

MshC; MshC ligase; Cys:GlcN-Ins ligase; mycothiol ligase

Systematic name:

L-cysteine:1-O-(2-amino-2-deoxy-α-D-glucopyranosyl)-1D-myo-inositol ligase (AMP-forming)

Comments:

This enzyme is a key enzyme in the biosynthesis of mycothiol, a small molecular weight thiol found in Mycobacteria spp. and other actinomycetes. Mycothiol plays a fundamental role in these organisms by helping to provide protection from the effects of reactive oxygen species and electrophiles, including many antibiotics. The enzyme may represent a novel target for new classes of antituberculars [2].

Links to other databases:

References:

1.	Fan, F., Luxenburger, A., Painter, G.F. and Blanchard, J.S. Steady-state and pre-steady-state kinetic analysis of Mycobacterium smegmatis cysteine ligase (MshC). Biochemistry 46 (2007) 11421–11429. [DOI] [PMID: 17848100]
2.	Gutierrez-Lugo, M.T., Newton, G.L., Fahey, R.C. and Bewley, C.A. Cloning, expression and rapid purification of active recombinant mycothiol ligase as B1 immunoglobulin binding domain of streptococcal protein G, glutathione-S-transferase and maltose binding protein fusion proteins in Mycobacterium smegmatis. Protein Expr. Purif. 50 (2006) 128–136. [DOI] [PMID: 16908186]
3.	Tremblay, L.W., Fan, F., Vetting, M.W. and Blanchard, J.S. The 1.6 Å crystal structure of Mycobacterium smegmatis MshC: the penultimate enzyme in the mycothiol biosynthetic pathway. Biochemistry 47 (2008) 13326–13335. [DOI] [PMID: 19053270]

[EC 6.3.1.13 created 2009]

6.3.2.31

Accepted name:

coenzyme F₄₂₀-0:L-glutamate ligase

Reaction:

GTP + coenzyme F₄₂₀-0 + L-glutamate = GDP + phosphate + coenzyme F₄₂₀-1

For diagram of coenzyme F₄₂₀ biosynthesis, click here

Glossary:

coenzyme F₄₂₀ = N-(N-{O-[5-(8-hydroxy-2,4-dioxo-2,3,4,10-tetrahydropyrimido[4,5-b]quinolin-10-yl)-5-deoxy-L-ribityl-1-phospho]-(S)-lactyl}-γ-L-glutamyl)-L-glutamate

Other name(s):

CofE-AF; MJ0768; CofE

Systematic name:

L-glutamate:coenzyme F₄₂₀-0 ligase (GDP-forming)

Comments:

This protein catalyses the successive addition of two glutamate residues to factor F₄₂₀ (coenzyme F₄₂₀) by two distinct and independent reactions. In the reaction described here the enzyme attaches a glutamate via its α-amine group to F₄₂₀-0. In the second reaction (EC 6.3.2.34, coenzyme F₄₂₀-1:γ-L-glutamate ligase) it catalyses the addition of a second L-glutamate residue to the γ-carboxyl of the first glutamate.

Links to other databases:

References:

1.	Li, H., Graupner, M., Xu, H. and White, R.H. CofE catalyzes the addition of two glutamates to F₄₂₀-0 in F₄₂₀ coenzyme biosynthesis in Methanococcus jannaschii. Biochemistry 42 (2003) 9771–9778. [DOI] [PMID: 12911320]
2.	Nocek, B., Evdokimova, E., Proudfoot, M., Kudritska, M., Grochowski, L.L., White, R.H., Savchenko, A., Yakunin, A.F., Edwards, A. and Joachimiak, A. Structure of an amide bond forming F₄₂₀:γ-glutamyl ligase from Archaeoglobus fulgidus — a member of a new family of non-ribosomal peptide synthases. J. Mol. Biol. 372 (2007) 456–469. [DOI] [PMID: 17669425]

[EC 6.3.2.31 created 2010]

6.3.2.34

Accepted name:

coenzyme F₄₂₀-1:γ-L-glutamate ligase

Reaction:

GTP + coenzyme F₄₂₀-1 + L-glutamate = GDP + phosphate + coenzyme γ-F₄₂₀-2

For diagram of coenzyme F₄₂₀ biosynthesis, click here

Glossary:

coenzyme F₄₂₀ = N-(N-{O-[5-(8-hydroxy-2,4-dioxo-2,3,4,10-tetrahydropyrimido[4,5-b]quinolin-10-yl)-5-deoxy-L-ribityl-1-phospho]-(S)-lactyl}-γ-L-glutamyl)-L-glutamate

Other name(s):

F₄₂₀:γ-glutamyl ligase; CofE-AF; MJ0768; CofE

Systematic name:

L-glutamate:coenzyme F₄₂₀-1 ligase (GDP-forming)

Comments:

This protein catalyses the successive addition of two glutamate residues to factor 420 (coenzyme F₄₂₀) by two distinct and independent reactions. In the first reaction (EC 6.3.2.31, coenzyme F₄₂₀-0:L-glutamate ligase) the enzyme attaches a glutamate via its α-amine group to F₄₂₀-0. In the second reaction, which is described here, the enzyme catalyses the addition of a second L-glutamate residue to the γ-carboxyl of the first glutamate.

Links to other databases: