Enzyme Nomenclature

Continued from EC 6.3.3 to EC 6.3.5

EC 6.4 and EC 6.5

Sections

EC 6.4 Forming Carbon—Carbon Bonds
EC 6.5 Forming Phosphoric Ester Bonds
EC 6.6 Forming Nitrogen—Metal Bonds


EC 6.4 Forming Carbon—Carbon Bonds

Contents

EC 6.4.1.1 pyruvate carboxylase
EC 6.4.1.2 acetyl-CoA carboxylase
EC 6.4.1.3 propionyl-CoA carboxylase
EC 6.4.1.4 methylcrotonoyl-CoA carboxylase
EC 6.4.1.5 geranoyl-CoA carboxylase
EC 6.4.1.6 acetone carboxylase
EC 6.4.1.7 2-oxoglutarate carboxylase
EC 6.4.1.8 acetophenone carboxylase


Entries

EC 6.4.1.1

Accepted name: pyruvate carboxylase

Reaction: ATP + pyruvate + HCO3- = ADP + phosphate + oxaloacetate

Other name(s): pyruvic carboxylase

Systematic name: pyruvate:carbon-dioxide ligase (ADP-forming)

Comments: A biotinyl-protein containing manganese (animal tissues) or zinc (yeast). The animal enzyme requires acetyl-CoA.

Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9014-19-1

References:

1. McClure, W.R., Lardy, H.A. and Kneifel, H.P. Rat liver pyruvate carboxylase. I. Preparation, properties, and cation specificity. J. Biol. Chem. 246 (1971) 3569-3578. [PMID: 5578910]

2. Scrutton, M.C., Young, M.R. and Utter, M.F. Pyruvate carboxylase from baker's yeast. The presence of bound zinc. J. Biol. Chem. 245 (1970) 6220-6227. [PMID: 5484476]

3. Seubert, W. and Remberger, U. Renigung und Wirkungsweise der Pyruvatcarboxylase aus Pseudomonas citronellolis. Biochem. Z. 334 (1961) 401-414.

4. Utter, M.F. and Keech, D.B. Pyruvate carboxylase. I. Nature of the reaction. J. Biol. Chem. 238 (1963) 2603-2608.

[EC 6.4.1.1 created 1961]

EC 6.4.1.2

Accepted name: acetyl-CoA carboxylase

Reaction: ATP + acetyl-CoA + HCO3- = ADP + phosphate + malonyl-CoA

For diagram of reaction click here (another example).

Other name(s): acetyl coenzyme A carboxylase

Systematic name: acetyl-CoA:carbon-dioxide ligase (ADP-forming)

Comments: A biotinyl-protein. Also catalyses transcarboxylation; the plant enzyme also carboxylates propanonyl-CoA and butanoyl-CoA.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9023-93-2

References:

1. Hatch, M.D. and Stumpf, P.K. Fat metabolism in higher plants. XVI. Acetyl coenzyme A carboxylase and acyl coenzyme A-malonyl coenzyme A transcarboxylase from wheat germ. J. Biol. Chem. 236 (1961) 2879-2885.

2. Matsuhashi, M., Matsuhashi, S. and Lynen, F. Zur Biosynthese der Fettsäuren. V. Die Acetyl-CoA Carboxylase aus Rattenleber und ihre Aktivierung durch Citronsäure. Biochem. Z. 340 (1964) 263-289.

3. Matsuhashi, M., Matsuhashi, S., Numa, S. and Lynen, F. [On the biosynthesis of fatty acids. IV. Acetyl-CoA carboxylase from yeast.] Biochem. Z. 340 (1964) 243-262.

4. Vagelos, P. Regulation of fatty acid biosynthesis. Curr. Top. Cell. Regul. 4 (1971) 119-166.

5. Wakil, S.J. A malonic acid derivative as an intermediate in fatty acid synthesis. J. Am. Chem. Soc. 80 (1958) 6465 only.

[EC 6.4.1.2 created 1961]

EC 6.4.1.3

Accepted name: propionyl-CoA carboxylase

Reaction: ATP + propanoyl-CoA + HCO3- = ADP + phosphate + (S)-methylmalonyl-CoA

For diagram of reaction click here (another example).

Systematic name: propanoyl-CoA:carbon-dioxide ligase (ADP-forming)

Other name(s): propionyl coenzyme A carboxylase

Comments: A biotinyl-protein. Also carboxylates butanoyl-CoA and catalyses transcarboxylation.

Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9023-94-3

References:

1. Kaziro, Y., Ochoa, S., Warner, R.C. and Chen, J.-Y. Metabolism of propionic acid in animal tissues. VIII. Crystalline propionyl carboxylase. J. Biol. Chem. 236 (1961) 1917-1923.

2. Lane, M.D., Halenz, D.R., Kosow, D.P. and Hegre, C.S. Further studies on mitochondrial propionyl carboxylase. J. Biol. Chem. 235 (1960) 3082-3086.

3. Meyer, H., Nevaldine, B. and Meyer, F. Acyl-coenzyme A carboxylase of the free-living nematode Turbatrix aceti. 1. Its isolation and molecular characteristics. Biochemistry 17 (1978) 1822-1827. [PMID: 656363]

4. Moss, J. and Lane, M.D. The biotin-dependent enzymes. Adv. Enzymol. Relat. Areas Mol. Biol. 35 (1971) 321-442. [PMID: 4150153]

5. Vagelos, P. Regulation of fatty acid biosynthesis. Curr. Top. Cell. Regul. 4 (1971) 119-166.

[EC 6.4.1.3 created 1961, modified 1983]

EC 6.4.1.4

Accepted name: methylcrotonoyl-CoA carboxylase

Reaction: ATP + 3-methylcrotonoyl-CoA + HCO3- = ADP + phosphate + 3-methylglutaconyl-CoA

Other name(s): methylcrotonyl coenzyme A carboxylase; β-methylcrotonyl coenzyme A carboxylase; β-methylcrotonyl CoA carboxylase; methylcrotonyl-CoA carboxylase

Systematic name: 3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming)

Comments: A biotinyl-protein.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9023-95-4

References:

1. Knappe, J., Schlegel, H.-G. and Lynen, F. Zur biochemischen Funktion des Biotins. I. Die Beteilligung der β-Methyl-crotonyl-Carboxylase an der Bildung von β-Hydroxy-β-methyl-glutaryl-CoA from β-Hydroxy-isovaleryl-CoA. Biochem. Z. 335 (1961) 101-122.

2. Lynen, F., Knappe, J., Lorch, E., Jütting, G., Ringelmann, E. and Lachance, J.-P. Zur biochemischen Funktion des Biotins. II. Reinigung und Wirkungsweise der β-Methyl-crotonyl-Carboxlase. Biochem. Z. 335 (1961) 123-166.

3. Rilling, H.C. and Coon, M.J. The enzymatic isomerization of α-methylvinylacetyl coenzyme A and the specificity of a bacterial α-methylcrotonyl coenzyme A carboxylase. J. Biol. Chem. 235 (1960) 3087-3092.

4. Vagelos, P. Regulation of fatty acid biosynthesis. Curr. Top. Cell. Regul. 4 (1971) 119-166.

[EC 6.4.1.4 created 1961]

EC 6.4.1.5

Accepted name: geranoyl-CoA carboxylase

Reaction: ATP + geranoyl-CoA + HCO3- = ADP + phosphate + 3-(4-methylpent-3-en-1-yl)pent-2-enedioyl-CoA

Other name(s): geranoyl coenzyme A carboxylase; geranyl-CoA carboxylase

Systematic name: geranoyl-CoA:carbon-dioxide ligase (ADP-forming)

Comments: A biotinyl-protein. Also carboxylates dimethylpropenoyl-CoA and farnesoyl-CoA.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, UM-BBD, CAS registry number: 37324-35-9

References:

1. Seubert, W., Fass, E. and Remberger, U. Untersuchungen über den bakteriellen Abbau von Isoprenoiden. III. Reinigung und Eigenschaften der Geranylcarboxylase. Biochem. Z. 338 (1963) 265-275.

[EC 6.4.1.5 created 1972]

EC 6.4.1.6

Accepted name: acetone carboxylase

Reaction: acetone + CO2 + ATP + 2 H2O = acetoacetate + AMP + 2 phosphate

Systematic name: acetone:carbon-dioxide ligase (AMP-forming)

Comments: Requires Mg2+ and ATP. The enzyme from Xanthobacter sp. strain Py2 also carboxylates butan-2-one to 3-oxopentanoate.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 189258-15-9

References:

1. Sluis, M.K. and Ensign, S.A. Purification and characterization of acetone carboxylase from Xanthobacter strain Py2. Proc. Natl. Acad. Sci. USA 94 (1997) 8456-8461. [PMID: 9237998]

[EC 6.4.1.6 created 2001]

EC 6.4.1.7

Accepted name: 2-oxoglutarate carboxylase

Reaction: ATP + 2-oxoglutarate + HCO3- = ADP + phosphate + oxalosuccinate

For diagram click here.

Glossary: oxalosuccinate = 1-oxopropane-1,2,3-tricarboxylate

Other name(s): oxalosuccinate synthetase; carboxylating factor for ICDH (incorrect); CFI; OGC

Comments: A biotin-containing enzyme that requires Mg2+ for activity. It was originally thought [1] that this enzyme was a promoting factor for the carboxylation of 2-oxoglutarate by EC 1.1.1.41, isocitrate dehydrogenase (NAD+), but this has since been disproved [2]. The product of the reaction is unstable and is quickly converted into isocitrate by the action of EC 1.1.1.41 [2].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 60382-75-4

References:

1. Aoshima, M., Ishii, M. and Igarashi, Y. A novel biotin protein required for reductive carboxylation of 2-oxoglutarate by isocitrate dehydrogenase in Hydrogenobacter thermophilus TK-6. Mol. Microbiol. 51 (2004) 791-798. [PMID: 14731279]

2. Aoshima, M. and Igarashi, Y. A novel oxalosuccinate-forming enzyme involved in the reductive carboxylation of 2-oxoglutarate in Hydrogenobacter thermophilus TK-6. Mol. Microbiol. 62 (2006) 748-759. [PMID: 17076668]

[EC 6.4.1.7 created 2006]

EC 6.4.1.8

Accepted name: acetophenone carboxylase

Reaction: 2 ATP + acetophenone + HCO3- + H2O + H+ = 2 ADP + 2 phosphate + 3-oxo-3-phenylpropanoate

Systematic name: acetophenone:carbon-dioxide ligase (ADP-forming)

Comments: The enzyme is involved in anaerobic degradation of ethylbenzene. No activity with acetone, butanone, 4-hydroxy-acetophenone or 4-amino-acetophenone.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, UM-BBD, CAS registry number:

References:

1. Jobst, B., Schuhle, K., Linne, U. and Heider, J. ATP-dependent carboxylation of acetophenone by a novel type of carboxylase. J. Bacteriol. 192 (2010) 1387-1394. [PMID: 20047908]

[EC 6.4.1.8 created 2011]


EC 6.5 Forming Phosphoric Ester Bonds

Contents

EC 6.5.1.1 DNA ligase (ATP)
EC 6.5.1.2 DNA ligase (NAD+)
EC 6.5.1.3 RNA ligase (ATP)
EC 6.5.1.4 RNA 3'-terminal-phosphate cyclase (ATP)
EC 6.5.1.5 RNA 3'-terminal-phosphate cyclase (GTP)
EC 6.5.1.6 DNA ligase (ATP or NAD+)
EC 6.5.1.7 DNA ligase (ATP, ADP or GTP)
EC 6.5.1.8 3'-phosphate/5'-hydroxy nucleic acid ligase

Entries

EC 6.5.1.1

Accepted name: DNA ligase (ATP)

Reaction: ATP + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + diphosphate (overall reaction)
(1a) ATP + [DNA ligase]-L-lysine = [DNA ligase]-N6-(5'-adenylyl)-L-lysine + diphosphate
(1b) [DNA ligase]-N6-(5'-adenylyl)-L-lysine + 5'-phospho-(deoxyribonucleotide)m = 5'-(5'-diphosphoadenosine)-(deoxyribonucleotide)m + [DNA ligase]-L-lysine
(1c) (deoxyribonucleotide)n-3'-hydroxyl + 5'-(5'-diphosphoadenosine)-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP

Other name(s): polydeoxyribonucleotide synthase (ATP); polynucleotide ligase (ambiguous); sealase; DNA repair enzyme (ambiguous); DNA joinase (ambiguous); DNA ligase (ambiguous); deoxyribonucleic ligase (ambiguous); deoxyribonucleate ligase (ambiguous); DNA-joining enzyme (ambiguous); deoxyribonucleic-joining enzyme (ambiguous); deoxyribonucleic acid-joining enzyme (ambiguous); deoxyribonucleic repair enzyme (ambiguous); deoxyribonucleic joinase (ambiguous); deoxyribonucleic acid ligase (ambiguous); deoxyribonucleic acid joinase (ambiguous); deoxyribonucleic acid repair enzyme (ambiguous); poly(deoxyribonucleotide):poly(deoxyribonucleotide) ligase (AMP-forming)

Systematic name: poly(deoxyribonucleotide)-3'-hydroxyl:5'-phospho-poly(deoxyribonucleotide) ligase (ATP)

Comments: The enzyme catalyses the ligation of DNA strands with 3'-hydroxyl and 5'-phosphate termini, forming a phosphodiester and sealing certain types of single-strand breaks in duplex DNA. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by ATP, forming a phosphoramide bond between adenylate and a lysine residue. The adenylate group is then transferred to the 5'-phosphate terminus of the substrate, forming the capped structure 5'-(5'-diphosphoadenosine)-[DNA]. Finally, the enzyme catalyses a nucleophilic attack of the 3'-OH terminus on the capped terminus, which results in formation of the phosphodiester bond and release of the adenylate. RNA can also act as substrate, to some extent. cf. EC 6.5.1.2, DNA ligase (NAD+), EC 6.5.1.6, DNA ligase (ATP or NAD+), and EC 6.5.1.7, DNA ligase (ATP, ADP or GTP).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9015-85-4

References:

1. Becker, A., Lyn, G., Gefter, M. and Hurwitz, J. The enzymatic repair of DNA. II. Characterization of phage-induced sealase. Proc. Natl. Acad. Sci. USA 58 (1967) 1996-2003. [PMID: 4295584]

2. Bertazzoni, U., Mathelet, M. and Campagnari, F. Purification and properties of a polynucleotide ligase from calf thymus glands. Biochim. Biophys. Acta 287 (1972) 404-414. [PMID: 4641251]

3. Weiss, B. and Richardson, C.C. Enzymatic breakage and joining of deoxyribonucleic acid. I. Repair of single-strand breaks in DNA by an enzyme system from Escherichia coli infected with T4 bacteriophage. Proc. Natl. Acad. Sci. USA 57 (1967) 1021-1028. [PMID: 5340583]

4. Howes, T.R. and Tomkinson, A.E. DNA ligase I, the replicative DNA ligase. Subcell. Biochem. 62 (2012) 327-341. [PMID: 22918593]

[EC 6.5.1.1 created 1972, modified 1976, modified 2016]

EC 6.5.1.2

Accepted name: DNA ligase (NAD+)

Reaction: NAD+ + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + β-nicotinamide D-nucleotide (overall reaction)
(1a) NAD+ + [DNA ligase]-L-lysine = [DNA ligase]-N6-(5'-adenylyl)-L-lysine + β-nicotinamide D-nucleotide
(1b) [DNA ligase]-N6-(5'-adenylyl)-L-lysine + 5'-phospho-(deoxyribonucleotide)m = 5'-(5'-diphosphoadenosine)-(deoxyribonucleotide)m + [DNA ligase]-L-lysine
(1c) (deoxyribonucleotide)n-3'-hydroxyl + 5'-(5'-diphosphoadenosine)-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP

Other name(s): polydeoxyribonucleotide synthase (NAD+); polynucleotide ligase (NAD+); DNA repair enzyme (ambiguous); DNA joinase (ambiguous); polynucleotide synthetase (nicotinamide adenine dinucleotide); deoxyribonucleic-joining enzyme (ambiguous); deoxyribonucleic ligase (ambiguous); deoxyribonucleic repair enzyme (ambiguous); deoxyribonucleic joinase (ambiguous); DNA ligase (ambiguous); deoxyribonucleate ligase (ambiguous); polynucleotide ligase (ambiguous); deoxyribonucleic acid ligase (ambiguous); polynucleotide synthetase (ambiguous); deoxyribonucleic acid joinase (ambiguous); DNA-joining enzyme (ambiguous); polynucleotide ligase (nicotinamide adenine dinucleotide); poly(deoxyribonucleotide):poly(deoxyribonucleotide) ligase (AMP-forming, NMN-forming)

Systematic name: poly(deoxyribonucleotide)-3'-hydroxyl:5'-phospho-poly(deoxyribonucleotide) ligase (NAD+)

Comments: The enzyme, typically found in bacteria, catalyses the ligation of DNA strands with 3'-hydroxyl and 5'-phosphate termini, forming a phosphodiester and sealing certain types of single-strand breaks in duplex DNA. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by NAD+, forming a phosphoramide bond between adenylate and a lysine residue. The adenylate group is then transferred to the 5'-phosphate terminus of the substrate, forming the capped structure 5'-(5'-diphosphoadenosine)-[DNA]. Finally, the enzyme catalyses a nucleophilic attack of the 3'-OH terminus on the capped terminus, which results in formation of the phosphodiester bond and release of the adenylate. RNA can also act as substrate, to some extent. cf. EC 6.5.1.1, DNA ligase (ATP), EC 6.5.1.6, DNA ligase (ATP or NAD+), and EC 6.5.1.7, DNA ligase (ATP, ADP or GTP).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37259-52-2

References:

1. Zimmerman, S.B., Little, J.W., Oshinsky, C.K. and Gellert, M. Enzymatic joining of DNA strands: a novel reaction of diphosphopyridine nucleotide. Proc. Natl. Acad. Sci. USA 57 (1967) 1841-1848. [PMID: 4291949]

2. Little, J.W., Zimmerman, S.B., Oshinsky, C.K. and Gellert, M. Enzymatic joining of DNA strands, II. An enzyme-adenylate intermediate in the dpn-dependent DNA ligase reaction. Proc. Natl. Acad. Sci. USA 58 (1967) 2004-2011. [PMID: 4295585]

3. Modorich, P. and Lehman, I.R. Deoxyribonucleic acid ligase. A steady state kinetic analysis of the reaction catalyzed by the enzyme from Escherichia coli. J. Biol. Chem. 248 (1973) 7502-7511. [PMID: 4355585]

4. Modrich, P., Anraku, Y. and Lehman, I.R. Deoxyribonucleic acid ligase. Isolation and physical characterization of the homogeneous enzyme from Escherichia coli. J. Biol. Chem. 248 (1973) 7495-7501. [PMID: 4355584]

5. Uphoff, S., Reyes-Lamothe, R., Garza de Leon, F., Sherratt, D.J. and Kapanidis, A.N. Single-molecule DNA repair in live bacteria. Proc. Natl. Acad. Sci. USA 110 (2013) 8063-8068. [PMID: 23630273]

[EC 6.5.1.2 created 1972, modified 1976, modified 2016]

EC 6.5.1.3

Accepted name: RNA ligase (ATP)

Reaction: ATP + (ribonucleotide)n-3'-hydroxyl + 5'-phospho-(ribonucleotide)m = (ribonucleotide)n+m + AMP + diphosphate (overall reaction)
(1a) ATP + [RNA ligase]-L-lysine = [RNA ligase]-N6-(5'-adenylyl)-L-lysine + diphosphate
(1b) [RNA ligase]-N6-(5'-adenylyl)-L-lysine + 5'-phospho-(ribonucleotide)m = 5'-(5'-diphosphoadenosine)-(ribonucleotide)m + [RNA ligase]-L-lysine
(1c) (ribonucleotide)n-3'-hydroxyl + 5'-(5'-diphosphoadenosine)-(ribonucleotide)m = (ribonucleotide)n+m + AMP

Other name(s): polyribonucleotide synthase (ATP); RNA ligase; polyribonucleotide ligase; ribonucleic ligase; poly(ribonucleotide):poly(ribonucleotide) ligase (AMP-forming)

Systematic name: poly(ribonucleotide)-3'-hydroxyl:5'-phospho-poly(ribonucleotide) ligase (ATP)

Comments: The enzyme catalyses the ligation of RNA strands with 3'-hydroxyl and 5'-phosphate termini, forming a phosphodiester and sealing certain types of single-strand breaks in RNA. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by ATP, forming a phosphoramide bond between adenylate and a lysine residue. The adenylate group is then transferred to the 5'-phosphate terminus of the substrate, forming the capped structure 5'-(5'-diphosphoadenosine)-[RNA]. Finally, the enzyme catalyses a nucleophilic attack of the 3'-OH terminus on the capped terminus, which results in formation of the phosphodiester bond and release of the adenylate.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37353-39-2

References:

1. Silber, R., Malathi, V.G. and Hurwitz, J. Purification and properties of bacteriophage T4-induced RNA ligase. Proc. Natl. Acad. Sci. USA 69 (1972) 3009-3013. [PMID: 4342972]

2. Cranston, J.W., Silber, R., Malathi, V.G. and Hurwitz, J. Studies on ribonucleic acid ligase. Characterization of an adenosine triphosphate-inorganic pyrophosphate exchange reaction and demonstration of an enzyme-adenylate complex with T4 bacteriophage-induced enzyme. J. Biol. Chem. 249 (1974) 7447-7456. [PMID: 4373468]

3. Sugino, A., Snoper, T.J. and Cozzarelli, N.R. Bacteriophage T4 RNA ligase. Reaction intermediates and interaction of substrates. J. Biol. Chem. 252 (1977) 1732-1738. [PMID: 320212]

4. Romaniuk, P.J. and Uhlenbeck, O.C. Joining of RNA molecules with RNA ligase. Methods Enzymol. 100 (1983) 52-59. [PMID: 6194411]

5. Ho, C.K., Wang, L.K., Lima, C.D. and Shuman, S. Structure and mechanism of RNA ligase. Structure 12 (2004) 327-339. [PMID: 14962393]

6. Nandakumar, J., Shuman, S. and Lima, C.D. RNA ligase structures reveal the basis for RNA specificity and conformational changes that drive ligation forward. Cell 127 (2006) 71-84. [PMID: 17018278]

[EC 6.5.1.3 created 1976, modified 2016]

EC 6.5.1.4

Accepted name: RNA 3'-terminal-phosphate cyclase (ATP)

Reaction: ATP + [RNA]-3'-(3'-phospho-ribonucleoside) = AMP + diphosphate + [RNA]-3'-(2',3'-cyclophospho)-ribonucleoside (overall reaction)
(1a) ATP + [RNA 3'-phosphate cyclase]-L-histidine = [RNA 3'-phosphate cyclase]-Nτ-(5'-adenylyl)-L-histidine + diphosphate
(1b) [RNA 3'-phosphate cyclase]-Nτ-(5'-adenylyl)-L-histidine + [RNA]-3'-(3'-phospho-ribonucleoside) = [RNA 3'-phosphate cyclase]-L-histidine + [RNA]-3'-ribonucleoside-3'-(5'-diphosphoadenosine)
(1c) [RNA]-3'-ribonucleoside-3'-(5'-diphosphoadenosine) = [RNA]-3'-(2',3'-cyclophospho)-ribonucleoside + AMP

Other name(s): rtcA (gene name); RNA cyclase (ambiguous); RNA-3'-phosphate cyclase (ambiguous)

Systematic name: RNA-3'-phosphate:RNA ligase (cyclizing, AMP-forming)

Comments: The enzyme converts the 3'-terminal phosphate of various RNA substrates into the 2',3'-cyclic phosphodiester in an ATP-dependent reaction. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by ATP, forming a phosphoramide bond between adenylate and a histidine residue [5,6]. The adenylate group is then transferred to the 3'-phosphate terminus of the substrate, forming the capped structure [RNA]-3'-(5'-diphosphoadenosine). Finally, the enzyme catalyses an attack of the vicinal O2' on the 3'-phosphorus, which results in formation of cyclic phosphate and release of the adenylate. The enzyme also has a polynucleotide 5' adenylylation activity [7]. cf. EC 6.5.1.5, RNA 3'-terminal-phosphate cyclase (GTP).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 85638-41-1

References:

1. Filipowicz, W., Konarska, M., Gross, H.J. and Shatkin, A.J. RNA 3'-terminal phosphate cyclase activity and RNA ligation in HeLa cell extract. Nucleic Acids Res. 11 (1983) 1405-1418. [PMID: 6828385]

2. Reinberg, D., Arenas, J. and Hurwitz, J. The enzymatic conversion of 3'-phosphate terminated RNA chains to 2',3'-cyclic phosphate derivatives. J. Biol. Chem. 260 (1985) 6088-6097. [PMID: 2581947]

3. Genschik, P., Billy, E., Swianiewicz, M. and Filipowicz, W. The human RNA 3'-terminal phosphate cyclase is a member of a new family of proteins conserved in Eucarya, Bacteria and Archaea. EMBO J. 16 (1997) 2955-2967. [PMID: 9184239]

4. Genschik, P., Drabikowski, K. and Filipowicz, W. Characterization of the Escherichia coli RNA 3'-terminal phosphate cyclase and its σ54-regulated operon. J. Biol. Chem. 273 (1998) 25516-25526. [PMID: 9738023]

5. Billy, E., Hess, D., Hofsteenge, J. and Filipowicz, W. Characterization of the adenylation site in the RNA 3'-terminal phosphate cyclase from Escherichia coli. J. Biol. Chem. 274 (1999) 34955-34960. [PMID: 10574971]

6. Tanaka, N. and Shuman, S. Structure-activity relationships in human RNA 3'-phosphate cyclase. RNA 15 (2009) 1865-1874. [PMID: 19690099]

7. Chakravarty, A.K. and Shuman, S. RNA 3'-phosphate cyclase (RtcA) catalyzes ligase-like adenylylation of DNA and RNA 5'-monophosphate ends. J. Biol. Chem. 286 (2011) 4117-4122. [PMID: 21098490]

8. Das, U. and Shuman, S. 2'-Phosphate cyclase activity of RtcA: a potential rationale for the operon organization of RtcA with an RNA repair ligase RtcB in Escherichia coli and other bacterial taxa. RNA 19 (2013) 1355-1362. [PMID: 23945037]

[EC 6.5.1.4 created 1986, modified 1989, modified 2013, modified 2016]

EC 6.5.1.5

Accepted name: RNA 3'-terminal-phosphate cyclase (GTP)

Reaction: GTP + [RNA]-3'-(3'-phospho-ribonucleoside) = GMP + diphosphate + [RNA]-3'-(2',3'-cyclophospho)-ribonucleoside (overall reaction)
(1a) GTP + [RNA 3'-phosphate cyclase]-L-histidine = 5'-guanosyl [RNA 3'-phosphate cyclase]-Nτ-phosphono-L-histidine + diphosphate
(1b) 5'-guanosyl [RNA 3'-phosphate cyclase]-Nτ-phosphono-L-histidine + [RNA]-3'-(3'-phospho-ribonucleoside) = [RNA 3'-phosphate cyclase]-L-histidine + [RNA]-3'-ribonucleoside-3'-(5'-diphosphoguanosine)
(1c) [RNA]-3'-ribonucleoside-3'-(5'-diphosphoguanosine) = [RNA]-3'-(2',3'-cyclophospho)-ribonucleoside + GMP

Other name(s): Pf-Rtc; RNA-3'-phosphate cyclase (GTP)

Systematic name: RNA-3'-phosphate:RNA ligase (cyclizing, GMP-forming)

Comments: The enzyme, which is specific for GTP, was characterized from the archaeon Pyrococcus furiosus. The enzyme converts the 3'-terminal phosphate of various RNA substrates into the 2',3'-cyclic phosphodiester in a GTP-dependent reaction. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by GTP, forming a phosphoramide bond between guanylate and a histidine residue. The guanylate group is then transferred to the 3'-phosphate terminus of the substrate, forming the capped structure [RNA]-3'-(5'-diphosphoguanosine). Finally, the enzyme catalyses an attack of the vicinal O2' on the 3'-phosphorus, which results in formation of cyclic phosphate and release of the guanylate. cf. EC 6.5.1.4, RNA-3'-phosphate cyclase (ATP).

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

References:

1. Sato, A., Soga, T., Igarashi, K., Takesue, K., Tomita, M. and Kanai, A. GTP-dependent RNA 3'-terminal phosphate cyclase from the hyperthermophilic archaeon Pyrococcus furiosus. Genes Cells 16 (2011) 1190-1199. [PMID: 22074260]

[EC 6.5.1.5 created 2013, modified 2016]

EC 6.5.1.6

Accepted name: DNA ligase (ATP or NAD+)

Reaction: (1) ATP + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + diphosphate (overall reaction)
(1a) ATP + [DNA ligase]-L-lysine = 5'-adenosyl [DNA ligase]-Nε-phosphono-L-lysine + diphosphate
(1b) 5'-adenosyl [DNA ligase]-Nε-phosphono-L-lysine + 5'-phospho-(deoxyribonucleotide)m = 5'-(5'-diphosphoadenosine)-(deoxyribonucleotide)m + [DNA ligase]-L-lysine
(1c) (deoxyribonucleotide)n-3'-hydroxyl + 5'-(5'-diphosphoadenosine)-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP
(2) NAD+ + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + β-nicotinamide D-nucleotide (overall reaction)
(2a) NAD+ + [DNA ligase]-L-lysine = 5'-adenosyl [DNA ligase]-Nε-phosphono-L-lysine + β-nicotinamide D-nucleotide
(2b) 5'-adenosyl [DNA ligase]-Nε-phosphono-L-lysine + 5'-phospho-(deoxyribonucleotide)m = 5'-(5'-diphosphoadenosine)-(deoxyribonucleotide)m + [DNA ligase]-L-lysine
(2c) (deoxyribonucleotide)n-3'-hydroxyl + 5'-(5'-diphosphoadenosine)-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP

Systematic name: poly(deoxyribonucleotide)-3'-hydroxyl:5'-phospho-poly(deoxyribonucleotide) ligase (ATP or NAD+)

Comments: The enzymes from the archaea Thermococcus fumicolans and Thermococcus onnurineus show high activity with either ATP or NAD+, and significantly lower activity with TTP, GTP, and CTP. The enzyme catalyses the ligation of DNA strands with 3'-hydroxyl and 5'-phosphate termini, forming a phosphodiester and sealing certain types of single-strand breaks in duplex DNA. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by ATP or NAD+, forming a phosphoramide bond between adenylate and a lysine residue. The adenylate group is then transferred to the 5'-phosphate terminus of the substrate, forming the capped structure 5'-(5'-diphosphoadenosine)-[DNA]. Finally, the enzyme catalyses a nucleophilic attack of the 3'-OH terminus on the capped terminus, which results in formation of the phosphodiester bond and release of the adenylate. Different from EC 6.5.1.1, DNA ligase (ATP), EC 6.5.1.2, DNA ligase (NAD+) and EC 6.5.1.7, DNA ligase (ATP, ADP or GTP).

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

References:

1. Rolland, J.L., Gueguen, Y., Persillon, C., Masson, J.M. and Dietrich, J. Characterization of a thermophilic DNA ligase from the archaeon Thermococcus fumicolans. FEMS Microbiol. Lett. 236 (2004) 267-273. [PMID: 15251207]

2. Kim, Y.J., Lee, H.S., Bae, S.S., Jeon, J.H., Yang, S.H., Lim, J.K., Kang, S.G., Kwon, S.T. and Lee, J.H. Cloning, expression, and characterization of a DNA ligase from a hyperthermophilic archaeon Thermococcus sp. Biotechnol. Lett. 28 (2006) 401-407. [PMID: 16614906]

[EC 6.5.1.6 created 2014, modified 2016]

EC 6.5.1.7

Accepted name: DNA ligase (ATP, ADP or GTP)

Reaction: (1) ATP + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + diphosphate (overall reaction)
(1a) ATP + [DNA ligase]-L-lysine = 5'-adenosyl [DNA ligase]-Nε-phosphono-L-lysine + diphosphate
(1b) 5'-adenosyl [DNA ligase]-Nε-phosphono-L-lysine + 5'-phospho-(deoxyribonucleotide)m = 5'-(5'-diphosphoadenosine)-(deoxyribonucleotide)m + [DNA ligase]-L-lysine
(1c) (deoxyribonucleotide)n-3'-hydroxyl + 5'-(5'-diphosphoadenosine)-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP
(2) ADP + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + Pi (overall reaction)
(2a) ADP + [DNA ligase]-L-lysine = 5'-adenosyl [DNA ligase]-Nε-phosphono-L-lysine + Pi
(2b) 5'-adenosyl [DNA ligase]-Nε-phosphono-L-lysine + 5'-phospho-(deoxyribonucleotide)m = 5'-(5'-diphosphoadenosine)-(deoxyribonucleotide)m + [DNA ligase]-L-lysine
(2c) (deoxyribonucleotide)n-3'-hydroxyl + 5'-(5'-diphosphoadenosine)-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP
(3) GTP + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + GMP + diphosphate (overall reaction)
(3a) GTP + [DNA ligase]-L-lysine = 5'-guanosyl [DNA ligase]-Nε-phosphono-L-lysine + diphosphate
(3b) 5'-guanosyl [DNA ligase]-Nε-phosphono-L-lysine + 5'-phospho-(deoxyribonucleotide)m = 5'-(5'-diphosphoguanosine)-(deoxyribonucleotide)m + [DNA ligase]-L-lysine
(3c) (deoxyribonucleotide)n-3'-hydroxyl + 5'-(5'-diphosphoguanosine)-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + GMP

Systematic name: poly(deoxyribonucleotide)-3'-hydroxyl:5'-phospho-poly(deoxyribonucleotide) ligase (ATP, ADP or GTP)

Comments: The enzymes from the archaea Hyperthermus butylicus and Sulfophobococcus zilligii are active with ATP, ADP or GTP. They show no activity with NAD+. The enzyme catalyses the ligation of DNA strands with 3'-hydroxyl and 5'-phosphate termini, forming a phosphodiester and sealing certain types of single-strand breaks in duplex DNA. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by ATP, ADP, or GTP, forming a phosphoramide bond between adenylate/guanylate and a lysine residue. The nucleotide is then transferred to the 5'-phosphate terminus of the substrate, forming the capped structure 5'-(5'-diphosphoadenosine/guanosine)-[DNA]. Finally, the enzyme catalyses a nucleophilic attack of the 3'-OH terminus on the capped terminus, which results in formation of the phosphodiester bond and release of the nucleotide. Different from EC 6.5.1.1, DNA ligase (ATP), and EC 6.5.1.6, DNA ligase (ATP or NAD+), which cannot utilize GTP.

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

References:

1. Sun, Y., Seo, M.S., Kim, J.H., Kim, Y.J., Kim, G.A., Lee, J.I., Lee, J.H. and Kwon, S.T. Novel DNA ligase with broad nucleotide cofactor specificity from the hyperthermophilic crenarchaeon Sulfophobococcus zilligii: influence of ancestral DNA ligase on cofactor utilization. Environ Microbiol 10 (2008) 3212-3224. [PMID: 18647334]

2. Kim, J.H., Lee, K.K., Sun, Y., Seo, G.J., Cho, S.S., Kwon, S.H. and Kwon, S.T. Broad nucleotide cofactor specificity of DNA ligase from the hyperthermophilic crenarchaeon Hyperthermus butylicus and its evolutionary significance. Extremophiles 17 (2013) 515-522. [PMID: 23546841]

[EC 6.5.1.7 created 2014, modified 2016]

EC 6.5.1.8

Accepted name: 3'-phosphate/5'-hydroxy nucleic acid ligase

Reaction: (1) (ribonucleotide)n-3'-phosphate + 5'-hydroxy-(ribonucleotide)m + GTP = (ribonucleotide)n+m + GMP + diphosphate (overall reaction)
(1a) GTP + [RNA ligase]-L-histidine = 5'-guanosyl [RNA ligase]-Nτ-phosphono-L-histidine + diphosphate
(1b) 5'-guanosyl [RNA ligase]-Nτ-phosphono-L-histidine + (ribonucleotide)n-3'-phosphate = (ribonucleotide)n-3'-(5'-diphosphoguanosine) + [RNA ligase]-L-histidine
(1c) (ribonucleotide)n-3'-(5'-diphosphoguanosine) + 5'-hydroxy-(ribonucleotide)m = (ribonucleotide)n+m + GMP
(2) (ribonucleotide)n-2',3'-cyclophosphate + 5'-hydroxy-(ribonucleotide)m + GTP + H2O = (ribonucleotide)n+m + GMP + diphosphate (overall reaction)
(2a) (ribonucleotide)n-2',3'-cyclophosphate + H2O = (ribonucleotide)n-3'-phosphate
(2b) GTP + [RNA ligase]-L-histidine = 5'-guanosyl [RNA ligase]-Nτ-phosphono-L-histidine + diphosphate
(2c) 5'-guanosyl [RNA ligase]-Nτ-phosphono-L-histidine + (ribonucleotide)n-3'-phosphate = (ribonucleotide)n-3'-(5'-diphosphoguanosine) + [RNA ligase]-L-histidine
(2d) (ribonucleotide)n-3'-(5'-diphosphoguanosine) + 5'-hydroxy-(ribonucleotide)m = (ribonucleotide)n+m + GMP

Other name(s): rtcB (gene name)

Systematic name: poly(ribonucleotide)-3'-phosphate:5'-hydroxy-poly(ribonucleotide) ligase (GMP-forming)

Comments: The enzyme is a GTP- and Mn2+-dependent 3'-5' nucleic acid ligase with the ability to join RNA with 3'-phosphate or 2',3'-cyclic-phosphate ends to RNA with 5'-hydroxy ends. It can also join DNA with 3'-phosphate ends to DNA with 5'-hydroxy ends, provided the DNA termini are unpaired [6]. The enzyme is found in members of all three kingdoms of life, and is essential in metazoa for the splicing of intron-containing tRNAs. The reaction follows a three-step mechanism with initial activation of the enzyme by GTP hydrolysis, forming a phosphoramide bond between the guanylate and a histidine residue. The guanylate group is transferred to the 3'-phosphate terminus of the substrate, forming the capped structure [DNA/RNA]-3'-(5'-diphosphoguanosine). When a suitable 5'-OH end is available, the enzyme catalyses an attack of the 5'-OH on the capped end to form a 3'-5' phosphodiester splice junction, releasing the guanylate. When acting on an RNA 2',3'-cyclic-phosphate, the enzyme cayalyses an additional reaction, hydrolysing the cyclic phosphate to a 3'-phosphate [9]. The metazoan enzyme requires activating cofactors in order to achieve multiple turnover catalysis [8].

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

References:

1. Tanaka, N., Meineke, B. and Shuman, S. RtcB, a novel RNA ligase, can catalyze tRNA splicing and HAC1 mRNA splicing in vivo. J. Biol. Chem. 286 (2011) 30253-30257. [PMID: 21757685]

2. Tanaka, N. and Shuman, S. RtcB is the RNA ligase component of an Escherichia coli RNA repair operon. J. Biol. Chem. 286 (2011) 7727-7731. [PMID: 21224389]

3. Tanaka, N., Chakravarty, A.K., Maughan, B. and Shuman, S. Novel mechanism of RNA repair by RtcB via sequential 2',3'-cyclic phosphodiesterase and 3'-phosphate/5'-hydroxyl ligation reactions. J. Biol. Chem. 286 (2011) 43134-43143. [PMID: 22045815]

4. Desai, K.K. and Raines, R.T. tRNA ligase catalyzes the GTP-dependent ligation of RNA with 3'-phosphate and 5'-hydroxyl termini. Biochemistry 51 (2012) 1333-1335. [PMID: 22320833]

5. Chakravarty, A.K., Subbotin, R., Chait, B.T. and Shuman, S. RNA ligase RtcB splices 3'-phosphate and 5'-OH ends via covalent RtcB-(histidinyl)-GMP and polynucleotide-(3')pp(5')G intermediates. Proc. Natl. Acad. Sci. USA 109 (2012) 6072-6077. [PMID: 22474365]

6. Chakravarty, A.K. and Shuman, S. The sequential 2',3'-cyclic phosphodiesterase and 3'-phosphate/5'-OH ligation steps of the RtcB RNA splicing pathway are GTP-dependent. Nucleic Acids Res. 40 (2012) 8558-8567. [PMID: 22730297]

7. Das, U., Chakravarty, A.K., Remus, B.S. and Shuman, S. Rewriting the rules for end joining via enzymatic splicing of DNA 3'-PO4 and 5'-OH ends. Proc. Natl. Acad. Sci. USA 110 (2013) 20437-20442. [PMID: 24218597]

8. Desai, K.K., Beltrame, A.L. and Raines, R.T. Coevolution of RtcB and Archease created a multiple-turnover RNA ligase. RNA 21 (2015) 1866-1872. [PMID: 26385509]

9. Maughan, W.P. and Shuman, S. Distinct contributions of enzymic functional groups to the 2',3'-cyclic phosphodiesterase, 3'-phosphate guanylylation, and 3'-ppG/5'-OH ligation steps of the Escherichia coli RtcB nucleic acid splicing pathway. J. Bacteriol. 198 (2016) 1294-1304. [PMID: 26858100]

[EC 6.5.1.8 created 2017]


EC 6.6 Forming nitrogen—metal bonds

EC 6.6.1 Forming coordination complexes

Contents

EC 6.6.1.1 magnesium chelatase
EC 6.6.1.2 cobaltochelatase


EC 6.6.1.1

Accepted name: magnesium chelatase

Reaction: ATP + protoporphyrin IX + Mg2+ + H2O = ADP + phosphate + Mg-protoporphyrin IX + 2 H+

For diagram of reaction click here (heme and chlorophyll biosynthesis).

Other name(s): protoporphyrin IX magnesium-chelatase; protoporphyrin IX Mg-chelatase; magnesium-protoporphyrin IX chelatase; magnesium-protoporphyrin chelatase; magnesium-chelatase; Mg-chelatase; Mg-protoporphyrin IX magnesio-lyase

Systematic name: Mg-protoporphyrin IX magnesium-lyase

Comments: This is the first committed step of chlorophyll biosynthesis and is a branchpoint of two major routes in the tetrapyrrole pathway.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9074-88-8

References:

1. Walker, C.J. and Weinstein, J.D. In vitro assay of the chlorophyll biosynthetic enzyme Mg-chelatase: resolution of the activity into soluble and membrane-bound fractions. Proc. Natl. Acad. Sci. USA 88 (1991) 5789-5793. [PMID: 11607197]

2. Walker, C.J. and Willows, R.D. Mechanism and regulation of Mg-chelatase. Biochem. J. 327 (1997) 321-333. [PMID: 9359397]

3. Fodje, M.N., Hansson, A., Hansson, M., Olsen, J.G., Gough, S., Willows, R.D. and Al-Karadaghi, S. Interplay between an AAA module and an integrin I domain may regulate the function of magnesium chelatase. J. Mol. Biol. 311 (2001) 111-122. [PMID: 11469861]

[EC 6.6.1.1 created 2003]

EC 6.6.1.2

Accepted name: cobaltochelatase

Reaction: ATP + hydrogenobyrinic acid a,c-diamide + Co2+ = ADP + phosphate + cob(II)yrinic acid a,c-diamide + H+

For diagram click here.

Other name(s): hydrogenobyrinic acid a,c-diamide cobaltochelatase; CobNST; CobN–CobST

Systematic name: hydrogenobyrinic-acid-a,c-diamide:cobalt cobalt-ligase (ADP-forming)

Comments: This enzyme, which forms part of the aerobic cobalamin biosynthesis pathway, is a type I chelatase, being heterotrimeric and ATP-dependent. It comprises two components, one of which corresponds to CobN and the other is composed of two polypeptides, specified by cobS and cobT in Pseudomonas denitrificans, and named CobST [1]. Hydrogenobyrinic acid is a very poor substrate. ATP can be replaced by dATP or CTP but the reaction proceeds more slowly. CobN exhibits a high affinity for hydrogenobyrinic acid a,c-diamide. The oligomeric protein CobST possesses at least one sulfhydryl group that is essential for ATP-binding. Once the Co2+ is inserted, the next step in the pathway ensures that the cobalt is ligated securely by reducing Co(II) to Co(I). This step is carried out by EC 1.16.8.1, cob(II)yrinic acid a,c-diamide reductase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 81295-49-0

References:

1. Debussche, L., Couder, M., Thibaut, D., Cameron, B., Crouzet, J. and Blanche, F. Assay, purification, and characterization of cobaltochelatase, a unique complex enzyme catalyzing cobalt insertion in hydrogenobyrinic acid a,c-diamide during coenzyme B12 biosynthesis in Pseudomonas denitrificans. J. Bacteriol. 174 (1992) 7445-7451. [PMID: 1429466]

2. Warren, M.J., Raux, E., Schubert, H.L. and Escalante-Semerena, J.C. The biosynthesis of adenosylcobalamin (vitamin B12). Nat. Prod. Rep. 19 (2002) 390-412. [PMID: 12195810]

[EC 6.6.1.2 created 2004]


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