Continued from EC 5.4
EC 5.5 Intramolecular Lyases
EC 5.6 Isomerases altering macromolecular conformation
EC 5.99 Other Isomerases
Accepted name: muconate cycloisomerase
Reaction: 2,5-dihydro-5-oxofuran-2-acetate = cis,cis-hexadienedioate
For diagram click here (another example).
Glossary: muconolactone = (2,5-dihydro-5-oxofuran-2-yl)acetate
cis,cis-hexadienedioate = (2Z,4Z)-hexa-2,4-dienedioate = cis,cis-muconate
Other name(s): muconate cycloisomerase I; cis,cis-muconate-lactonizing enzyme; cis,cis-muconate cycloisomerase; muconate lactonizing enzyme; 4-carboxymethyl-4-hydroxyisocrotonolactone lyase (decyclizing); CatB; MCI; 2,5-dihydro-5-oxofuran-2-acetate lyase (decyclizing)
Systematic name: 2,5-dihydro-5-oxofuran-2-acetate lyase (ring-opening)
Comments: Requires Mn2+. Also acts (in the reverse reaction) on 3-methyl-cis,cis-hexadienedioate and, very slowly, on cis,trans-hexadienedioate. Not identical with EC 5.5.1.7 (chloromuconate cycloisomerase) or EC 5.5.1.11 (dichloromuconate cycloisomerase).
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9023-72-7
References:
1. Ornston, L.N. The conversion of catechol and protocatechuate to β-ketoadipate by Pseudomonas putida. 3. Enzymes of the catechol pathway. J. Biol. Chem. 241 (1966) 3795-3799. [PMID: 5330966]
2. Ornston, L.N. Conversion of catechol and protocatechuate to β-ketoadipate (Pseudomonas putida). Methods Enzymol. 17A (1970) 529-549.
3. Sistrom, W.R. and Stanier, R.Y. The mechanism of formation of β-ketoadipic acid by bacteria. J. Biol. Chem. 210 (1954) 821-836.
Accepted name: 3-carboxy-cis,cis-muconate cycloisomerase
Reaction: 2-carboxy-2,5-dihydro-5-oxofuran-2-acetate = cis,cis-butadiene-1,2,4-tricarboxylate
For diagram click here (another example).
Other name(s): β-carboxymuconate lactonizing enzyme; 3-carboxymuconolactone hydrolase; 2-carboxy-2,5-dihydro-5-oxofuran-2-acetate lyase (decyclizing)
Systematic name: 2-carboxy-2,5-dihydro-5-oxofuran-2-acetate lyase (ring-opening)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9075-77-8
References:
1. Ornston, L.N. The conversion of catechol and protocatechuate to β-ketoadipate by Pseudomonas putida. II. Enzymes of the protocatechuate pathway. J. Biol. Chem. 241 (1966) 3787-3794. [PMID: 5916392]
2. Ornston, L.N. Conversion of catechol and protocatechuate to β-ketoadipate (Pseudomonas putida). Methods Enzymol. 17A (1970) 529-549.
Accepted name: tetrahydroxypteridine cycloisomerase
Reaction: tetrahydroxypteridine = xanthine-8-carboxylate
Systematic name: tetrahydroxypteridine lyase (isomerizing)
Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, CAS registry number: 37318-54-0
References:
1. McNutt, W.S. and Damle, S.P. Tetraoxypteridine isomerase. J. Biol. Chem. 239 (1964) 4272-4279.
Accepted name: inositol-3-phosphate synthase
Reaction: D-glucose 6-phosphate = 1D-myo-inositol 3-phosphate
EC 5.5.1.4 inositol-3-phosphate synthase (mechanism)
Other name(s): myo-inositol-1-phosphate synthase; D-glucose 6-phosphate cycloaldolase; inositol 1-phosphate synthatase; glucose 6-phosphate cyclase; inositol 1-phosphate synthetase; glucose-6-phosphate inositol monophosphate cycloaldolase; glucocycloaldolase; 1L-myo-inositol-1-phosphate lyase (isomerizing)
Systematic name: 1D-myo-inositol-3-phosphate lyase (isomerizing)
Comments: Requires NAD+, which dehydrogenates the -CHOH- group to -CO- at C-5 of the glucose 6-phosphate, making C-6 into an active methylene, able to condense with the -CHO at C-1. Finally, the enzyme-bound NADH reconverts C-5 into the -CHOH- form.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9032-95-5
References:
1. Eisenberg, F., Jr. D-Myoinositol 1-phosphate as product of cyclization of glucose 6-phosphate and substrate for a specific phosphatase in rat testis. J. Biol. Chem. 242 (1967) 1375-1382. [PMID: 4290245]
2. Sherman, W.R., Stewart, M.A. and Zinbo, M. Mass spectrometric study on the mechanism of D-glucose 6-phosphate-L-myo-inositol 1-phosphate cyclase. J. Biol. Chem. 244 (1969) 5703-5708. [PMID: 4310603]
3. Barnett, J.E.G. and Corina, D.L. The mechanism of glucose 6-phosphate-D-myo-inositol 1-phosphate cyclase of rat testis. The involvement of hydrogen atoms. Biochem. J. 108 (1968) 125-129. [PMID: 4297937]
4. Barnett, J.E.G., Rasheed, A. and Corina, D.L. Partial reactions of glucose 6-phosphate-1L-myo-inositol 1-phosphate cyclase. Biochem. J. 131 (1973) 21-30. [PMID: 4352864]
Accepted name: carboxy-cis,cis-muconate cyclase
Reaction: 3-carboxy-2,5-dihydro-5-oxofuran-2-acetate = 3-carboxy-cis,cis-muconate
For diagram click here.
Other name(s): 3-carboxymuconate cyclase; 3-carboxy-2,5-dihydro-5-oxofuran-2-acetate lyase (decyclizing)
Systematic name: 3-carboxy-2,5-dihydro-5-oxofuran-2-acetate lyase (ring-opening)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37318-55-1
References:
1. Gross, S.R., Gafford, R.D. and Tatum, E.L. The metabolism of protocatechuic acid by Neurospora. J. Biol. Chem. 219 (1956) 781-796.
Accepted name: chalcone isomerase
Reaction: A chalcone = a flavanone
See diagram for reaction in naringenin or liquiritigenin biosynthesis.
Other name(s): chalcone-flavanone isomerase; flavanone lyase (decyclizing)
Systematic name: flavanone lyase (ring-opening)
Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9073-57-8
References:
1. Moustafa, E. and Wong, E. Purification and properties of chalcone-flavanone isomerase from soya bean seed. Phytochemistry 6 (1967) 625-632.
Accepted name: chloromuconate cycloisomerase
Reaction: (2R)-2-chloro-2,5-dihydro-5-oxofuran-2-acetate = 3-chloro-cis,cis-muconate
For diagram click here.
Glossary: (2R)-2-chloro-2,5-dihydro-5-oxofuran-2-acetate = (+)-4-chloromuconolactone
3-chloro-cis,cis-muconate = (2E,4Z)-3-chlorohexa-2,4-dienedioate
Other name(s): muconate cycloisomerase II; 2-chloro-2,5-dihydro-5-oxofuran-2-acetate lyase (decyclizing); 2-chloro-2,5-dihydro-5-oxofuran-2-acetate lyase (ring-opening)
Systematic name: (2R)-2-chloro-2,5-dihydro-5-oxofuran-2-acetate lyase (ring-opening)
Comments: Requires Mn2+. The product of cycloisomerization of 3-chloro-cis,cis-muconate spontaneously eliminates chloride to produce cis-4-carboxymethylenebut-2-en-4-olide. Also acts (in the reverse direction) on 2-chloro-cis,cis-muconate. Not identical with EC 5.5.1.1 (muconate cycloisomerase) or EC 5.5.1.11 (dichloromuconate cycloisomerase).
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 95990-33-3
References:
1. Schmidt, E. and Knackmuss, H.-J. Chemical structure and biodegradability of halogenated aromatic compounds. Conversion of chlorinated muconic acids into maleoylacetic acid. Biochem. J. 192 (1980) 339-347. [PMID: 7305906]
2. Kaulmann, U., Kaschabek, S.R. and Schlomann, M. Mechanism of chloride elimination from 3-chloro- and 2,4-dichloro-cis,cis-muconate: new insight obtained from analysis of muconate cycloisomerase variant CatB-K169A. J. Bacteriol. 183 (2001) 4551-4561. [PMID: 11443090]
3. Kajander, T., Lehtio, L., Schlomann, M. and Goldman, A. The structure of Pseudomonas P51 Cl-muconate lactonizing enzyme: co-evolution of structure and dynamics with the dehalogenation function. Protein Sci. 12 (2003) 1855-1864. [PMID: 12930985]
Accepted name: (+)-bornyl diphosphate synthase
Reaction: geranyl diphosphate = (+)-bornyl diphosphate
For diagram of reaction click here and mechanism click here.
Glossary: (+)-bornyl diphosphate = (1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl diphosphate
Other name(s): bornyl pyrophosphate synthase (ambiguous); bornyl pyrophosphate synthetase (ambiguous); (+)-bornylpyrophosphate cyclase; geranyl-diphosphate cyclase (ambiguous); (+)-bornyl-diphosphate lyase (decyclizing)
Systematic name: (+)-bornyl-diphosphate lyase (ring-opening)
Comments: Requires Mg2+. The enzyme from Salvia officinalis (sage) can also use (3R)-linalyl diphosphate or more slowly neryl diphosphate in vitro [3]. The reaction proceeds via isomeration of geranyl diphosphate to (3R)-linalyl diphosphate. The oxygen and phosphorus originally linked to C-1 of geranyl diphosphate end up linked to C-2 of (+)-bornyl diphosphate [3]. cf. EC 5.5.1.22 [(–)-bornyl diphosphate synthase].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 72668-91-8
References:
1. Croteau, R. and Karp, F. Biosynthesis of monoterpenes: preliminary characterization of bornyl pyrophosphate synthetase from sage (Salvia officinalis) and demonstration that geranyl pyrophosphate is the preferred substrate for cyclization. Arch. Biochem. Biophys. 198 (1979) 512-522. [PMID: 42356]
2. Croteau, R., Gershenzon, J., Wheeler, C.J. and Satterwhite, D.M. Biosynthesis of monoterpenes: stereochemistry of the coupled isomerization and cyclization of geranyl pyrophosphate to camphane and isocamphane monoterpenes. Arch. Biochem. Biophys. 277 (1990) 374-381. [PMID: 2178556]
3. Croteau, R., Satterwhite, D.M., Cane, D.E. and Chang, C.C. Biosynthesis of monoterpenes. Enantioselectivity in the enzymatic cyclization of (+)- and (–)-linalyl pyrophosphate to (+)- and (–)-bornyl pyrophosphate. J. Biol. Chem. 261 (1986) 13438-13445. [PMID: 3759972]
4. Croteau, R., Felton, N.M. and Wheeler, C.J. Stereochemistry at C-1 of geranyl pyrophosphate and neryl pyrophosphate in the cyclization to (+)- and (–)-bornyl pyrophosphate. J. Biol. Chem. 260 (1985) 5956-5962. [PMID: 3997807]
5. Croteau, R.B., Shaskus, J.J., Renstrom, B., Felton, N.M., Cane, D.E., Saito, A. and Chang, C. Mechanism of the pyrophosphate migration in the enzymatic cyclization of geranyl and linalyl pyrophosphates to (+)- and (–)-bornyl pyrophosphates. Biochemistry 24 (1985) 7077-7085. [PMID: 4084562]
6. McGeady, P. and Croteau, R. Isolation and characterization of an active-site peptide from a monoterpene cyclase labeled with a mechanism-based inhibitor. Arch. Biochem. Biophys. 317 (1995) 149-155. [PMID: 7872777]
7. Wise, M.L., Savage, T.J., Katahira, E. and Croteau, R. Monoterpene synthases from common sage (Salvia officinalis). cDNA isolation, characterization, and functional expression of (+)-sabinene synthase, 1,8-cineole synthase, and (+)-bornyl diphosphate synthase. J. Biol. Chem. 273 (1998) 14891-14899. [PMID: 9614092]
8. Whittington, D.A., Wise, M.L., Urbansky, M., Coates, R.M., Croteau, R.B. and Christianson, D.W. Bornyl diphosphate synthase: structure and strategy for carbocation manipulation by a terpenoid cyclase. Proc. Natl. Acad. Sci. USA 99 (2002) 15375-15380. [PMID: 12432096]
9. Peters, R.J. and Croteau, R.B. Alternative termination chemistries utilized by monoterpene cyclases: chimeric analysis of bornyl diphosphate, 1,8-cineole, and sabinene synthases. Arch. Biochem. Biophys. 417 (2003) 203-211. [PMID: 12941302]
Accepted name: cycloeucalenol cycloisomerase
Reaction: cycloeucalenol = obtusifoliol
For diagram click here.
Other name(s): cycloeucalenol—obtusifoliol isomerase; cycloeucalenol lyase (cyclopropane-decyclizing)
Systematic name: cycloeucalenol lyase (cyclopropane-ring opening)
Comments: Opens the cyclopropane ring of a number of related 4α-methyl-9β-19-cyclosterols, but not those with a 4β-methyl group, with formation of an 8(9) double bond. Involved in the synthesis of plant sterols.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 60496-19-7
References:
1. Heintz, R. and Benveniste, P. Plant sterol metabolism. Enzymatic cleavage of the 9β,19β-cyclopropane ring of cyclopropyl sterols in bramble tissue cultures. J. Biol. Chem. 249 (1974) 4267-4274. [PMID: 4369016]
2. Rahier, A., Schmitt, P. and Benveniste, P. 7-oxo-24ξ(28)-dihydrocycloeucalenol, a potent inhibitor of plant sterol biosynthesis. Phytochemistry 21 (1982) 1969-1974.
Accepted name: α-pinene-oxide decyclase
Reaction: α-pinene oxide = (Z)-2-methyl-5-isopropylhexa-2,5-dienal
Other name(s): α-pinene oxide lyase; α-pinene-oxide lyase (decyclizing)
Systematic name: α-pinene-oxide lyase (ring-opening)
Comments: Both rings of pinene are cleaved in the reaction.
Links to other databases: BRENDA, EAWAG-BBD , EXPASY, KEGG, Metacyc, CAS registry number: 112692-50-9
References:
1. Griffiths, E.T., Harries, P.C., Jeffcoat, R. and Trudgill, P.W. Purification and properties of α-pinene oxide lyase from Nocardia sp. strain P18.3. J. Bacteriol. 169 (1987) 4980-4983. [PMID: 3667522]
Accepted name: dichloromuconate cycloisomerase
Reaction: 2,4-dichloro-2,5-dihydro-5-oxofuran-2-acetate = 2,4-dichloro-cis,cis-muconate
For diagram click here.
Other name(s): 2,4-dichloro-2,5-dihydro-5-oxofuran-2-acetate lyase (decyclizing)
Systematic name: 2,4-dichloro-2,5-dihydro-5-oxofuran-2-acetate lyase (ring-opening)
Comments: Requires Mn2+. The product of cycloisomerization of dichloro-cis,cis-muconate spontaneously eliminates chloride to produce cis-4-carboxymethylene-3-chlorobut-2-en-4-olide. Also acts, in the reverse direction, on cis,cis-muconate and its monochloro-derivatives, but with lower affinity. Not identical with EC 5.5.1.1 (muconate cycloisomerase) or EC 5.5.1.7 (chloromuconate cycloisomerase).
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, CAS registry number: 126904-95-8
References:
1. Kuhm, A.E., Schlömann, M., Knackmuss, H.-J. and Pieper, D.H. Purification and characterization of dichloromuconate cycloisomerase from Alcaligenes eutrophus JMP 134. Biochem. J. 266 (1990) 877-883. [PMID: 2327971]
Accepted name: copalyl diphosphate synthase
Reaction: geranylgeranyl diphosphate = (+)-copalyl diphosphate
For diagram of reaction click here.
Other name(s): (+)-copalyl-diphosphate lyase (decyclizing)
Systematic name: (+)-copalyl-diphosphate lyase (ring-opening)
Comments: In some plants, such as Salvia miltiorrhiza, this enzyme is monofunctional. In other plants this activity is often a part of a bifunctional enzyme. For example, in Selaginella moellendorffii this activity is catalysed by a bifunctional enzyme that also catalyses EC 4.2.3.131, miltiradiene synthase, while in the tree Abies grandis (grand fir) it is catalysed by a bifunctional enzyme that also catalyses EC 4.2.3.18, abietadiene synthase.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 157972-08-2
References:
1. Peters, R.J., Ravn, M.M., Coates, R.M. and Croteau, R.B. Bifunctional abietadiene synthase: free diffusive transfer of the (+)-copalyl diphosphate intermediate between two distinct active sites. J. Am. Chem. Soc. 123 (2001) 8974-8978. [PMID: 11552804]
2. Sugai, Y., Ueno, Y., Hayashi, K., Oogami, S., Toyomasu, T., Matsumoto, S., Natsume, M., Nozaki, H. and Kawaide, H. Enzymatic 13C labeling and multidimensional NMR analysis of miltiradiene synthesized by bifunctional diterpene cyclase in Selaginella moellendorffii. J. Biol. Chem. 286 (2011) 42840-42847. [PMID: 22027823]
3. Peters, R.J. and Croteau, R.B. Abietadiene synthase catalysis: mutational analysis of a prenyl diphosphate ionization-initiated cyclization and rearrangement. Proc. Natl. Acad. Sci. USA 99 (2002) 580-584. [PMID: 11805316]
4. Ravn, M.M., Peters, R.J., Coates, R.M. and Croteau, R. Mechanism of abietadiene synthase catalysis: stereochemistry and stabilization of the cryptic pimarenyl carbocation intermediates. J. Am. Chem. Soc. 124 (2002) 6998-7006. [PMID: 12059223]
5. Peters, R.J. and Croteau, R.B. Abietadiene synthase catalysis: conserved residues involved in protonation-initiated cyclization of geranylgeranyl diphosphate to (+)-copalyl diphosphate. Biochemistry 41 (2002) 1836-1842. [PMID: 11827528]
Accepted name: ent-copalyl diphosphate synthase
Reaction: geranylgeranyl diphosphate = ent-copalyl diphosphate
For diagram of reaction, click here.
Other name(s): ent-kaurene synthase A; ent-kaurene synthetase A; ent-CDP synthase; ent-copalyl-diphosphate lyase (decyclizing)
Systematic name: ent-copalyl-diphosphate lyase (ring-opening)
Comments: Part of a bifunctional enzyme involved in the biosynthesis of kaurene. See also EC 4.2.3.19 (ent-kaurene synthase)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9055-64-5
References:
1. Fall, R.R., West, C.A. Purification and properties of kaurene synthetase from Fusarium moniliforme. J. Biol. Chem. 246 (1971) 6913-6928. [PMID: 4331199]
2. Sun, T.P. and Kamiya, Y. The Arabidopsis GA1 locus encodes the cyclase ent-kaurene synthetase A of gibberellin biosynthesis. Plant Cell 6 (1994) 1509-1518. [PMID: 7994182]
3. Kawaide, H., Imai, R., Sassa, T. and Kamiya, Y. Ent-kaurene synthase from the fungus Phaeosphaeria sp. L487. cDNA isolation, characterization, and bacterial expression of a bifunctional diterpene cyclase in fungal gibberellin biosynthesis. J. Biol. Chem. 272 (1997) 21706-21712. [PMID: 9268298]
4. Toyomasu, T., Kawaide, H., Ishizaki, A., Shinoda, S., Otsuka, M., Mitsuhashi, W. and Sassa, T. Cloning of a full-length cDNA encoding ent-kaurene synthase from Gibberella fujikuroi: functional analysis of a bifunctional diterpene cyclase. Biosci. Biotechnol. Biochem. 64 (2000) 660-664. [PMID: 10803977]
Accepted name: syn-copalyl diphosphate synthase
Reaction: geranylgeranyl diphosphate = 9α-copalyl diphosphate
For diagram of reaction, click here
Glossary: syn-copalyl diphosphate = 9α-copalyl diphosphate
Other name(s): OsCyc1; OsCPSsyn; syn-CPP synthase; syn-copalyl diphosphate synthase; 9α-copalyl-diphosphate lyase (decyclizing)
Systematic name: 9α-copalyl-diphosphate lyase (ring-opening)
Comments: Requires a divalent metal ion, preferably Mg2+, for activity. This class II terpene synthase produces syn-copalyl diphosphate, a precursor of several rice phytoalexins, including oryzalexin S and momilactones A and B. Phytoalexins are diterpenoid secondary metabolites that are involved in the defense mechanism of the plant, and are produced in response to pathogen attack through the perception of elicitor signal molecules such as chitin oligosaccharide, or after exposure to UV irradiation. The enzyme is constitutively expressed in the roots of plants where one of its products, momilactone B, acts as an allelochemical (a molecule released into the environment to suppress the growth of neighbouring plants). In other tissues the enzyme is upregulated by conditions that stimulate the biosynthesis of phytoalexins.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Otomo, K., Kenmoku, H., Oikawa, H., Konig, W.A., Toshima, H., Mitsuhashi, W., Yamane, H., Sassa, T. and Toyomasu, T. Biological functions of ent- and syn-copalyl diphosphate synthases in rice: key enzymes for the branch point of gibberellin and phytoalexin biosynthesis. Plant J. 39 (2004) 886-893. [PMID: 15341631]
2. Xu, M., Hillwig, M.L., Prisic, S., Coates, R.M. and Peters, R.J. Functional identification of rice syn-copalyl diphosphate synthase and its role in initiating biosynthesis of diterpenoid phytoalexin/allelopathic natural products. Plant J. 39 (2004) 309-318. [PMID: 15255861]
Accepted name: terpentedienyl-diphosphate synthase
Reaction: geranylgeranyl diphosphate = terpentedienyl diphosphate
Glossary: terpentedienyl diphosphate = (2E)-3-methyl-5-[(1R,2R,4aS,8aS)-1,2,4a,5-tetramethyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl]pent-2-en-1-yl diphosphate
For diagram of reaction click here.
Other name(s): terpentedienol diphosphate synthase; Cyc1; clerodadienyl diphosphate synthase; terpentedienyl-diphosphate lyase (decyclizing)
Systematic name: terpentedienyl-diphosphate lyase (ring-opening)
Comments: Requires Mg2+. Contains a DXDD motif, which is a characteristic of diterpene cylases whose reactions are initiated by protonation at the 14,15-double bond of geranylgeranyl diphosphate (GGDP) [2]. The triggering proton is lost at the end of the cyclization reaction [3]. The product of the reaction, terpentedienyl diphosphate, is the substrate for EC 4.2.3.36, terpentetriene synthase and is a precursor of the diterpenoid antibiotic terpentecin.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Dairi, T., Hamano, Y., Kuzuyama, T., Itoh, N., Furihata, K. and Seto, H. Eubacterial diterpene cyclase genes essential for production of the isoprenoid antibiotic terpentecin. J. Bacteriol. 183 (2001) 6085-6094. [PMID: 11567009]
2. Hamano, Y., Kuzuyama, T., Itoh, N., Furihata, K., Seto, H. and Dairi, T. Functional analysis of eubacterial diterpene cyclases responsible for biosynthesis of a diterpene antibiotic, terpentecin. J. Biol. Chem. 277 (2002) 37098-37104. [PMID: 12138123]
3. Eguchi, T., Dekishima, Y., Hamano, Y., Dairi, T., Seto, H. and Kakinuma, K. A new approach for the investigation of isoprenoid biosynthesis featuring pathway switching, deuterium hyperlabeling, and 1H NMR spectroscopy. The reaction mechanism of a novel streptomyces diterpene cyclase. J. Org. Chem. 68 (2003) 5433-5438. [PMID: 12839434]
Accepted name: halimadienyl-diphosphate synthase
Reaction: geranylgeranyl diphosphate = tuberculosinyl diphosphate
For diagram of rection click here
Glossary: tuberculosinyl diphosphate = halima-5,13-dien-15-yl diphosphate
Other name(s): Rv3377c; halimadienyl diphosphate synthase; tuberculosinol diphosphate synthase; halima-5(6),13-dien-15-yl-diphosphate lyase (cyclizing); halima-5,13-dien-15-yl-diphosphate lyase (decyclizing)
Systematic name: halima-5,13-dien-15-yl-diphosphate lyase (ring-opening)
Comments: Requires Mg2+ for activity. This enzyme is found in pathogenic prokaryotes such as Mycobacterium tuberculosis but not in non-pathogens such as Mycobacterium smegmatis so may play a role in pathogenicity. The product of the reaction is subsequently dephosphorylated yielding tuberculosinol (halima-5,13-dien-15-ol).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Nakano, C., Okamura, T., Sato, T., Dairi, T. and Hoshino, T. Mycobacterium tuberculosis H37Rv3377c encodes the diterpene cyclase for producing the halimane skeleton. Chem. Commun. (Camb.) (2005) 1016-1018. [PMID: 15719101]
Accepted name: (S)-β-macrocarpene synthase
Reaction: (S)-β-bisabolene = (S)-β-macrocarpene
For diagram of reaction click here and mechanism click here.
Other name(s): TPS6; TPS11; (S)-β-macrocarpene lyase (decyclizing)
Systematic name: (S)-β-macrocarpene lyase (ring-opening)
Comment:The synthesis of (S)-β-macrocarpene from (2E,6E)-farnesyl diphosphate proceeds in two steps. The first step is the cyclization to (S)-β-bisabolene (cf. EC 4.2.3.55, (S)-β-bisabolene synthase). The second step is the isomerization to (S)-β-macrocarpene. Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Kollner, T.G., Schnee, C., Li, S., Svatos, A., Schneider, B., Gershenzon, J. and Degenhardt, J. Protonation of a neutral (S)-β-bisabolene intermediate is involved in (S)-β-macrocarpene formation by the maize sesquiterpene synthases TPS6 and TPS11. J. Biol. Chem. 283 (2008) 20779-20788. [PMID: 18524777]
Accepted name: lycopene ε-cyclase
Reaction: carotenoid ψ-end group = carotenoid ε-end group
For diagram of reaction click here and mechanism click here.
Other name(s): CrtL-e; LCYe; carotenoid ψ-end group lyase (decyclizing)
Systematic name: carotenoid ψ-end group lyase (ring-opening)
Comments: The carotenoid lycopene has the ψ-end group at both ends. When acting on one end, this enzyme forms δ-carotene. When acting on both ends, it forms ε-carotene.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Cunningham, F.X., Jr. and Gantt, E. One ring or two? Determination of ring number in carotenoids by lycopene ε-cyclases. Proc. Natl. Acad. Sci. USA 98 (2001) 2905-2910. [PMID: 11226339]
2. Stickforth, P., Steiger, S., Hess, W.R. and Sandmann, G. A novel type of lycopene ε-cyclase in the marine cyanobacterium Prochlorococcus marinus MED4. Arch. Microbiol. 179 (2003) 409-415. [PMID: 12712234]
Accepted name: lycopene β-cyclase
Reaction: carotenoid ψ-end group = carotenoid β-end group
For diagram of reaction click here, and here click here, and mechanism click here.
Other name(s): CrtL; CrtL-b; CrtY; LCYb; carotenoid β-end group lyase (decyclizing)
Systematic name: carotenoid β-end group lyase (ring-opening)
Comments: The enzyme is a non-redox flavoprotein, containing FADH2 that is used for stabilization of a transition state. Lycopene has a ψ-end group at both ends. When acting on one end, the enzyme forms γ-carotene. When acting on both ends it forms β-carotene. It also acts on neurosporene to give β-zeacarotene.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Cunningham, F.X., Jr., Chamovitz, D., Misawa, N., Gantt, E. and Hirschberg, J. Cloning and functional expression in Escherichia coli of a cyanobacterial gene for lycopene cyclase, the enzyme that catalyzes the biosynthesis of β-carotene. FEBS Lett. 328 (1993) 130-138. [PMID: 8344419]
2. Cunningham, F.X., Jr., Sun, Z., Chamovitz, D., Hirschberg, J. and Gantt, E. Molecular structure and enzymatic function of lycopene cyclase from the cyanobacterium Synechococcus sp strain PCC7942. Plant Cell 6 (1994) 1107-1121. [PMID: 7919981]
3. Hugueney, P., Badillo, A., Chen, H.C., Klein, A., Hirschberg, J., Camara, B. and Kuntz, M. Metabolism of cyclic carotenoids: a model for the alteration of this biosynthetic pathway in Capsicum annuum chromoplasts. Plant J. 8 (1995) 417-424. [PMID: 7550379]
4. Pecker, I., Gabbay, R., Cunningham, F.X., Jr. and Hirschberg, J. Cloning and characterization of the cDNA for lycopene β-cyclase from tomato reveals decrease in its expression during fruit ripening. Plant Mol. Biol. 30 (1996) 807-819. [PMID: 8624411]
5. Hornero-Mendez, D. and Britton, G. Involvement of NADPH in the cyclization reaction of carotenoid biosynthesis. FEBS Lett. 515 (2002) 133-136. [PMID: 11943208]
6. Maresca, J.A., Graham, J.E., Wu, M., Eisen, J.A. and Bryant, D.A. Identification of a fourth family of lycopene cyclases in photosynthetic bacteria. Proc. Natl. Acad. Sci. USA 104 (2007) 11784-11789. [PMID: 17606904]
7. Yu, Q., Schaub, P., Ghisla, S., Al-Babili, S., Krieger-Liszkay, A. and Beyer, P. The lycopene cyclase CrtY from Pantoea ananatis (formerly Erwinia uredovora) catalyzes an FADred-dependent non-redox reaction. J. Biol. Chem. 285 (2010) 12109-12120. [PMID: 20178989]
Accepted name: prosolanapyrone-III cycloisomerase
Reaction: prosolanapyrone III = (–)-solanapyrone A
For diagram of reaction click here
Glossary: prosolanapyrone III = 4-methoxy-2-oxo-6-(1E,7E,9E)-undeca-1,7,9-trien-1-yl-2H-pyran-3-carboxaldehyde
(–)-solanapyrone A = 4-methoxy-6-((1R,2S,4aR,8aR)-2-methyl-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl)-2-oxo-2H-pyran-3-carboxaldehyde
Other name(s): Sol5 (ambiguous); SPS (ambiguos); solanapyrone synthase (bifunctional enzyme: prosolanapyrone II oxidase/prosolanapyrone III cyclosiomerase)
Systematic name: prosolanapyrone-III:(–)-solanapyrone A isomerase
Comments: The enzyme is involved in the biosynthesis of the phytotoxin solanapyrone in some fungi. The bifunctional enzyme catalyses the oxidation of prosolanapyrone II and the subsequent Diels Alder cycloisomerization of the product prosolanapyrone III to (–)-solanapyrone A (cf. EC 1.1.3.42, prosolanapyrone II oxidase).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Kasahara, K., Miyamoto, T., Fujimoto, T., Oguri, H., Tokiwano, T., Oikawa, H., Ebizuka, Y. and Fujii, I. Solanapyrone synthase, a possible Diels-Alderase and iterative type I polyketide synthase encoded in a biosynthetic gene cluster from Alternaria solani. Chembiochem. 11 (2010) 1245-1252. [PMID: 20486243]
2. Katayama, K., Kobayashi, T., Oikawa, H., Honma, M. and Ichihara, A. Enzymatic activity and partial purification of solanapyrone synthase: first enzyme catalyzing Diels-Alder reaction. Biochim. Biophys. Acta 1384 (1998) 387-395. [PMID: 9659400]
3. Katayama, K., Kobayashi, T., Chijimatsu, M., Ichihara, A. and Oikawa, H. Purification and N-terminal amino acid sequence of solanapyrone synthase, a natural Diels-Alderase from Alternaria solani. Biosci. Biotechnol. Biochem. 72 (2008) 604-607. [PMID: 18256508]
[EC 5.5.1.21 Deleted entry: copal-8-ol diphosphate synthase. This enzyme was discovered at the public-review stage to have been misclassified and so was withdrawn. See EC 4.2.1.133, copal-8-ol diphosphate hydratase. (EC 5.5.1.21 created 2012, deleted 2012)]
Accepted name: (–)-bornyl diphosphate synthase
Reaction: geranyl diphosphate = (–)-bornyl diphosphate
For diagram of reaction click here.
Glossary: (–)-bornyl diphosphate = (2R,4S)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl diphosphate
Other name(s): bornyl pyrophosphate synthase (ambiguous); bornyl pyrophosphate synthetase (ambiguous); (–)-bornyl pyrophosphate cyclase; bornyl diphosphate synthase; geranyl-diphosphate cyclase (ambiguous); (–)-bornyl-diphosphate lyase (decyclizing)
Systematic name: (–)-bornyl-diphosphate lyase (ring-opening)
Comments: Requires Mg2+. The enzyme from Tanacetum vulgare (tansey) can also use (3S)-linalyl diphosphate or more slowly neryl diphosphate in vitro. The reaction proceeds via isomeration of geranyl diphosphate to (3S)-linalyl diphosphate [3]. The oxygen and phosphorus originally linked to C-1 of geranyl diphosphate end up linked to C-2 of (–)-bornyl diphosphate [4]. cf. EC 5.5.1.8 (+)-bornyl diphosphate synthase.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Croteau, R., Gershenzon, J., Wheeler, C.J. and Satterwhite, D.M. Biosynthesis of monoterpenes: stereochemistry of the coupled isomerization and cyclization of geranyl pyrophosphate to camphane and isocamphane monoterpenes. Arch. Biochem. Biophys. 277 (1990) 374-381. [PMID: 2178556]
2. Croteau, R. and Shaskus, J. Biosynthesis of monoterpenes: demonstration of a geranyl pyrophosphate:(–)-bornyl pyrophosphate cyclase in soluble enzyme preparations from tansy (Tanacetum vulgare). Arch. Biochem. Biophys. 236 (1985) 535-543. [PMID: 3970524]
3. Croteau, R., Felton, N.M. and Wheeler, C.J. Stereochemistry at C-1 of geranyl pyrophosphate and neryl pyrophosphate in the cyclization to (+)- and (–)-bornyl pyrophosphate. J. Biol. Chem. 260 (1985) 5956-5962. [PMID: 3997807]
4. Croteau, R.B., Shaskus, J.J., Renstrom, B., Felton, N.M., Cane, D.E., Saito, A. and Chang, C. Mechanism of the pyrophosphate migration in the enzymatic cyclization of geranyl and linalyl pyrophosphates to (+)- and (–)-bornyl pyrophosphates. Biochemistry 24 (1985) 7077-7085. [PMID: 4084562]
5. Adam, K.P. and Croteau, R. Monoterpene biosynthesis in the liverwort Conocephalum conicum: demonstration of sabinene synthase and bornyl diphosphate synthase. Phytochemistry 49 (1998) 475-480. [PMID: 9747540]
Accepted name: aklanonic acid methyl ester cyclase
Reaction: aklaviketone = methyl aklanonate
For diagram of reaction click here.
Glossary: aklaviketone = methyl (1R,2R)-2-ethyl-2,5,7-trihydroxy-4,6,11-trioxo-1,2,3,4,6,11-hexahydrotetracene-1-carboxylate
methyl aklanonate = methyl [4,5-dihydroxy-9,10-dioxo-3-(3-oxopentanoyl)-9,10-dihydroanthracen-2-yl]acetate
Other name(s): dauD (gene name); aknH (gene name); dnrD (gene name); methyl aklanonate cyclase; methyl aklanonate-aklaviketone isomerase (cyclizing); aklaviketone lyase (decyclizing)
Systematic name: aklaviketone lyase (ring-opening)
Comments: The enzyme is involved in the biosynthesis of aklaviketone, an intermediate in the biosynthetic pathways leading to formation of several anthracycline antibiotics, including aclacinomycin, daunorubicin and doxorubicin.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Dickens, M.L., Ye, J. and Strohl, W.R. Analysis of clustered genes encoding both early and late steps in daunomycin biosynthesis by Streptomyces sp. strain C5. J. Bacteriol. 177 (1995) 536-543. [PMID: 7836284]
2. Kendrew, S.G., Katayama, K., Deutsch, E., Madduri, K. and Hutchinson, C.R. DnrD cyclase involved in the biosynthesis of doxorubicin: purification and characterization of the recombinant enzyme. Biochemistry 38 (1999) 4794-4799. [PMID: 10200167]
3. Kallio, P., Sultana, A., Niemi, J., Mantsala, P. and Schneider, G. Crystal structure of the polyketide cyclase AknH with bound substrate and product analogue: implications for catalytic mechanism and product stereoselectivity. J. Mol. Biol. 357 (2006) 210-220. [PMID: 16414075]
Accepted name: tocopherol cyclase
Reaction: (1) δ-tocopherol = 2-methyl-6-phytylbenzene-1,4-diol
(2) γ-tocopherol = 2,3-dimethyl-6-phytylbenzene-1,4-diol
(3) δ-tocotrienol = 6-geranylgeranyl-2-methylbenzene-1,4-diol
(4) γ-tocotrienol = 6-geranylgeranyl-2,3-dimethylbenzene-1,4-diol
For diagram of tocopherol biosynthesis, click here or tocotrienol biosynthesis click here
Other name(s): VTE1 (gene name); SXD1 (gene name); δ/γ-tocopherol lyase (decyclizing)
Systematic name: δ/γ-tocopherol lyase (ring-opening)
Comments: The enzyme has been described from plants and cyanobacteria. It has similar activity with all four listed benzoquinol substrates. Involved in the biosynthesis of vitamin E tocopherols and tocotrienols.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Porfirova, S., Bergmuller, E., Tropf, S., Lemke, R. and Dormann, P. Isolation of an Arabidopsis mutant lacking vitamin E and identification of a cyclase essential for all tocopherol biosynthesis. Proc. Natl. Acad. Sci. USA 99 (2002) 12495-12500. [PMID: 12213958]
2. Sattler, S.E., Cahoon, E.B., Coughlan, S.J. and DellaPenna, D. Characterization of tocopherol cyclases from higher plants and cyanobacteria. Evolutionary implications for tocopherol synthesis and function. Plant Physiol. 132 (2003) 2184-2195. [PMID: 12913173]
Accepted name: 3,6-anhydro-L-galactonate cycloisomerase
Reaction: 3,6-anhydro-L-galactonate = 2-dehydro-3-deoxy-L-galactonate
Other name(s): 3,6-anhydro-α-L-galactonate lyase (ring-opening); 3,6-anhydro-α-L-galactonate cycloisomerase
Systematic name: 3,6-anhydro-L-galactonate lyase (ring-opening)
Comments: The enzyme, characterized from the marine bacteria Vibrio sp. EJY3 and Postechiella marina M091, is involved in a degradation pathway for 3,6-anhydro-α-L-galactopyranose, a major component of the polysaccharides of red macroalgae.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Yun, E.J., Lee, S., Kim, H.T., Pelton, J.G., Kim, S., Ko, H.J., Choi, I.G. and Kim, K.H. The novel catabolic pathway of 3,6-anhydro-L-galactose, the main component of red macroalgae, in a marine bacterium. Environ. Microbiol. 17 (2015) 1677-1688. [PMID: 25156229]
2. Lee, S.B., Cho, S.J., Kim, J.A., Lee, S.Y., Kim, S.M. and Lim, H.S. Metabolic pathway of 3,6-anhydro-L-galactose in agar-degrading microorganisms. Biotechnol. Bioprocess Eng. 19 (2014) 866-878.
Accepted name: nogalonic acid methyl ester cyclase
Reaction: nogalaviketone = methyl nogalonate
For diagram of reaction click here.
Glossary: methyl nogalonate = methyl [4,5-dihydroxy-9,10-dioxo-3-(3-oxobutanoyl)-9,10-dihydroanthracen-2-yl]acetate
nogalaviketone = methyl 5,7-dihydroxy-2-methyl-4,6,11-trioxo-3,4,6,11-tetrahydrotetracene-1-carboxylate
Other name(s): methyl nogalonate cyclase; SnoaL (gene name); methyl nogalonate lyase (cyclizing)
Systematic name: nogalaviketone lyase (ring-opening)
Comments: The enzyme, characterized from the bacterium Streptomyces nogalater, is involved in the biosynthesis of the aromatic polyketide nogalamycin.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Sultana, A., Kallio, P., Jansson, A., Wang, J.S., Niemi, J., Mantsala, P. and Schneider, G. Structure of the polyketide cyclase SnoaL reveals a novel mechanism for enzymatic aldol condensation. EMBO J. 23 (2004) 1911-1921. [PMID: 15071504]
2. Sultana, A., Kallio, P., Jansson, A., Niemi, J., Mantsala, P. and Schneider, G. Crystallization and preliminary crystallographic data of SnoaL, a polyketide cyclase in nogalamycin biosynthesis. Acta Crystallogr. D Biol. Crystallogr. 60 (2004) 1118-1120. [PMID: 15159574]
Accepted name: D-galactarolactone cycloisomerase
Reaction: (1) D-galactaro-1,4-lactone = 5-dehydro-4-deoxy-D-glucarate
(2) D-glucaro-1,4-lactone = 5-dehydro-4-deoxy-D-glucarate
Other name(s): GCI
Systematic name: D-galactaro-1,4-lactone lyase (ring-opening)
Comments: The enzyme, characterized from the bacterium Agrobacterium fabrum strain C58, is involved in degradation of D-galacturonate and D-glucuronate. Activity with D-galactaro-1,4-lactone is 4-fold higher than with D-glucaro-1,4-lactone.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Andberg, M., Maaheimo, H., Boer, H., Penttila, M., Koivula, A. and Richard, P. Characterization of a novel Agrobacterium tumefaciens galactarolactone cycloisomerase enzyme for direct conversion of D-galactarolactone to 3-deoxy-2-keto-L-threo-hexarate. J. Biol. Chem. 287 (2012) 17662-17671. [PMID: 22493433]
2. Bouvier, J.T., Groninger-Poe, F.P., Vetting, M., Almo, S.C. and Gerlt, J.A. Galactaro δ-lactone isomerase: lactone isomerization by a member of the amidohydrolase superfamily. Biochemistry 53 (2014) 614-616. [PMID: 24450804]
Accepted name: (–)-kolavenyl diphosphate synthase
Reaction: geranylgeranyl diphosphate = (–)-kolavenyl diphosphate
For diagram of reaction click here
Glossary: (–)-kolavenyl diphosphate = (2E)-5-[(1R,2S,4aS,8aS)-1,2,4a,5-tetramethyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl]-3-methylpent-2-en-1-yl diposphate
Other name(s): SdKPS; TwTPS14; TwTPS10/KPS; SdCPS2; clerodienyl diphosphate synthase; CLPP
Systematic name: (–)-kolavenyl diphosphate lyase (ring-opening)
Comments: Isolated from the hallucinogenic plant Salvia divinorum (seer’s sage) and the medicinal plant Tripterygium wilfordii (thunder god vine).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Hansen, N.L., Heskes, A.M., Hamberger, B., Olsen, C.E., Hallstrom, B.M., Andersen-Ranberg, J. and Hamberger, B. The terpene synthase gene family in Tripterygium wilfordii harbors a labdane-type diterpene synthase among the monoterpene synthase TPS-b subfamily. Plant J. 89 (2017) 429-441. [PMID: 27801964]
2. Chen, X., Berim, A., Dayan, F.E. and Gang, D.R. A (–)-kolavenyl diphosphate synthase catalyzes the first step of salvinorin A biosynthesis in Salvia divinorum. J. Exp. Bot. 68 (2017) 1109-1122. [PMID: 28204567]
Accepted name: (+)-kolavenyl diphosphate synthase
Reaction: geranylgeranyl diphosphate = (+)-kolavenyl diphosphate
For diagram of reaction click here
Glossary: (+) kolavenyl diphosphate = (2E)-3-methyl-5-[(1R,2S,4aS,8aS)-1,2,4a,5-tetramethyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl]pent-2-en-1-yl diphosphate
Systematic name: (+)-kolavenyl-diphosphate lyase (ring-opening)
Comments: Isolated from the bacterium Herpetosiphon aurantiacus.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Nakano, C., Oshima, M., Kurashima, N. and Hoshino, T. Identification of a new diterpene biosynthetic gene cluster that produces O-methylkolavelool in Herpetosiphon aurantiacus. Chembiochem 16 (2015) 772-781. [PMID: 25694050]
Accepted name: labda-7,13-dienyl diphosphate synthase
Reaction: geranylgeranyl diphosphate = (13E)-labda-7,13-dien-15-yl diphosphate
For diagram of reaction click here
Other name(s): SCLAV_p0490
Systematic name: (13E)-labda-7,13-dien-15-yl-diphosphate lyase (ring-opening)
Comments: Isolated from the bacterium Streptomyces clavuligerus.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Yamada, Y., Komatsu, M. and Ikeda, H. Chemical diversity of labdane-type bicyclic diterpene biosynthesis in Actinomycetales microorganisms. J. Antibiot. (Tokyo) 69 (2016) 515-523. [PMID: 26814669]
Accepted name: hapalindole H synthase
Reaction: 3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole = hapalindole H
For diagram of reaction click here.
Glossary: hapalindole H = (6aR,9R,10R,10aR)-9-ethenyl-1-isocyano-6,6,9-trimethyl-2,6,6a,7,8,9,10,10a-decahydronaphtho[1,2,3-cd]indole
Other name(s): famC2 (gene name); famC3 (gene name)
Systematic name: 3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole cyclase (hapalindole H-forming)
Comments: The enzyme, characterized from the cyanobacterium Fischerella ambigua UTEX 1903, forms the core structure of the hapalindole family of alkaloids. The enzyme is a heterodimeric complex.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Li, S., Lowell, A.N., Newmister, S.A., Yu, F., Williams, R.M. and Sherman, D.H. Decoding cyclase-dependent assembly of hapalindole and fischerindole alkaloids. Nat. Chem. Biol. 13 (2017) 467-469. [PMID: 28288107]
Accepted name: 12-epi-hapalindole U synthase
Reaction: 3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole = 12-epi-hapalindole U
For diagram of reaction click here.
Glossary: 12-epi-hapalindole H = (6aR,9S,10R,10aR)-9-ethenyl-1-isocyano-6,6,9-trimethyl-2,6,6a,7,8,9,10,10a-decahydronaphtho[1,2,3-cd]indole
Other name(s): famC1 (gene name); HpiC1 (gene name)
Systematic name: 3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole cyclase (12-epi-hapalindole U-forming)
Comments: The enzyme, characterized from the cyanobacterium Fischerella ambigua UTEX 1903, forms the core structure of the 12-epi-hapalindole family of alkaloids.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Li, S., Lowell, A.N., Yu, F., Raveh, A., Newmister, S.A., Bair, N., Schaub, J.M., Williams, R.M. and Sherman, D.H. Hapalindole/ambiguine biogenesis Is mediated by a Cope rearrangement, C-C bond-forming cascade. J. Am. Chem. Soc. 137 (2015) 15366-15369. [PMID: 26629885]
Accepted name: 12-epi-fischerindole U synthase
Reaction: 3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole = 12-epi-fischerindole U
For diagram of reaction click here.
Glossary: 12-epi-fischerindole U = (6aS,9S,10R,10aS)-9-ethenyl-10-isocyano-6,6,9-trimethyl-5H,6aH,7H,8H,10H,10aH-indeno[2,1-b]indole
Other name(s): fisC (gene name); fimC5 (gene name)
Systematic name: 3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole cyclase (12-epi-fischerindole U-forming)
Comments: The enzyme, characterized from multiple species of the cyanobacterial genus Fischerella, participates in the biosynthesis of the terpenoid indole alkaloids 12-epi-fischerindoles.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Li, S., Lowell, A.N., Newmister, S.A., Yu, F., Williams, R.M. and Sherman, D.H. Decoding cyclase-dependent assembly of hapalindole and fischerindole alkaloids. Nat. Chem. Biol. 13 (2017) 467-469. [PMID: 28288107]
Accepted name: (+)-cis,trans-nepetalactol synthase
Reaction: (S)-8-oxocitronellyl enol = (+)-cis,trans-nepetalactol
For diagram of reaction click here.
Glossary: (S)-8-oxocitronellyl enol = (2E,6S,7E)-8-hydroxy-2,6-dimethylocta-2,7-dienal
(+)-cis,trans-nepetalactol = (+)-iridodial lactol = (4aS,7S,7aR)-4,7-dimethyl-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-1-ol
Other name(s): NEPS1 (gene name); NEPS2 (gene name)
Systematic name: (S)-8-oxocitronellyl enol cyclase [(+)-cis,trans-nepetalactol-forming]
Comments: The enzyme, characterized from the plant Nepeta mussinii, binds an NAD+ cofactor. The product is a precursor of (+)-cis,trans-nepetalactone, the primary ingredient responsible for the psychoactive effects catnip has on cats.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Lichman, B.R., Kamileen, M.O., Titchiner, G.R., Saalbach, G., Stevenson, C.EM., Lawson, D.M. and O'Connor, S.E. Uncoupled activation and cyclization in catmint reductive terpenoid biosynthesis. Nat. Chem. Biol. 15 (2019) 71-79. [PMID: 30531909]
2. Lichman, B.R., O'Connor, S.E. and Kries, H. Biocatalytic strategies towards [4+2] cycloadditions. Chemistry 25 (2019) 6864-6877. [PMID: 30664302]
Accepted name: (+)-cis,cis-nepetalactol synthase
Reaction: (S)-8-oxocitronellyl enol = (+)-cis,cis-nepetalactol
For diagram of reaction click here.
Glossary: (S)-8-oxocitronellyl enol = (2E,6S,7E)-8-hydroxy-2,6-dimethylocta-2,7-dienal
(+)-cis,cis-nepetalactol =(4aR,7S,7aS)-4,7-dimethyl-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-1-ol
Other name(s): NEPS3 (gene name)
Systematic name: (S)-8-oxocitronellyl enol cyclase [(+)-cis,cis-nepetalactol-forming]
Comments: The enzyme, characterized from the plant Nepeta mussinii, binds an NAD+ cofactor. The product is a precursor of (+)-cis,cis-nepetalactone, one of the stereoisomers responsible for the psychoactive effects catnip has on cats.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Lichman, B.R., Kamileen, M.O., Titchiner, G.R., Saalbach, G., Stevenson, C.EM., Lawson, D.M. and O'Connor, S.E. Uncoupled activation and cyclization in catmint reductive terpenoid biosynthesis. Nat. Chem. Biol. 15 (2019) 71-79. [PMID: 30531909]
2. Lichman, B.R., O'Connor, S.E. and Kries, H. Biocatalytic strategies towards [4+2] cycloadditions. Chemistry 25 (2019) 6864-6877. [PMID: 30664302]
Accepted name: hapalindole U synthase
Reaction: 3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole = hapalindole U
For diagram of reaction click here
Glossary: hapalindole U = (6aS,9R,10R,10aS)-10-isocyano-6,6,9-trimethyl-9-vinyl-2,6,6a,7,8,9,10,10a-octahydronaphtho[1,2,3-cd]indole
Other name(s): ambU1/ambU4 (gene names); famC4/famC1 (gene names)
Systematic name: 3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole cyclase (hapalindole U-forming)
Comments: Requires Ca2+. The enzyme, which belongs to the Stig cyclases, has been characterized from multiple species of the cyanobacterial genera Fischerella and Westiellopsis. Stig cyclases catalyse a three step process including a Cope rearrangement, 6-exo-trig cyclization and electrophilic aromatic substitution. The enzyme is a heterodimer of two different proteins (AmbU1 and AmbU4). On their own, AmbU1 catalyses a different reaction, producing 12-epi-hapalindole U (cf. EC 5.5.1.32, 12-epi-hapalindole U synthase) while AmbU4 appears to be inactive. Formation of hapalindole U leads to the biosynthesis of additional terpenoid indole alkaloids such as hapalindole G, ambiguine H, and ambiguine A.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Zhu, Q. and Liu, X. Discovery of a calcium-dependent enzymatic cascade for the selective assembly of hapalindole-type alkaloids: on the biosynthetic origin of hapalindole U. Angew. Chem. Int. Ed. Engl. 56 (2017) 9062-9066. [PMID: 28626997]
2. Li, S., Newmister, S.A., Lowell, A.N., Zi, J., Chappell, C.R., Yu, F., Hohlman, R.M., Orjala, J., Williams, R.M. and Sherman, D.H. Control of stereoselectivity in diverse hapalindole metabolites is mediated by cofactor-induced combinatorial pairing of stig cyclases. Angew. Chem. Int. Ed. Engl. 59 (2020) 8166-8172. [PMID: 32052896]
EC 5.6.1 Enzymes altering polypeptide conformation or assembly
EC 5.6.2 Enzymes altering nucleic acid conformation
EC 5.6.1.1 microtubule-severing ATPase
EC 5.6.1.2 dynein ATPase
EC 5.6.1.3 plus-end-directed kinesin ATPase
EC 5.6.1.4 minus-end-directed kinesin ATPase
EC 5.6.1.5 proteasome ATPase
EC 5.6.1.6 channel-conductance-controlling ATPase
EC 5.6.1.7 chaperonin ATPase
EC 5.6.1.8 myosin ATPase
EC 5.6.1.9 (R)-2-hydroxyacyl-CoA dehydratase activating ATPase
Accepted name: microtubule-severing ATPase
Reaction: n ATP + n H2O + a microtubule = n ADP + n phosphate + (n+1) α/β tubulin heterodimers
Other name(s): katanin
Systematic name: ATP phosphohydrolase (tubulin-dimerizing)
Comments: A member of the AAA-ATPase family, active in splitting microtubules into tubulin dimers in the centrosome.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. McNally, F.J. and Vale, R.D. Identification of katanin, an ATPase that severs and disassembles stable microtubules. Cell 75 (1993) 419-429. [PMID: 8221885]
2. Hartman, J.J., Mahr, J., McNally, K., Okawa, K., Iwamatsu, A., Thomas, S., Cheesman, S., Heuser, J., Vale, R.D. and McNally, F.J. Katanin, a microtubule-severing protein, is a novel AAA ATPase that targets to the centrosome using a WD40-containing subunit. Cell 93 (1998) 277-287. [PMID: 9568719]
Accepted name: dynein ATPase
Reaction: ATP + H2O + a dynein associated with a microtubule at position n = ADP + phosphate + a dynein associated with a microtubule at position n-1 (toward the minus end)
Other name(s): dynein adenosine 5'-triphosphatase
Systematic name: ATP phosphohydrolase (tubulin-translocating)
Comments: A multisubunit protein complex associated with microtubules. Hydrolysis of ATP provides energy for the movement of organelles (endosomes, lysosomes, mitochondria) along microtubules to the centrosome towards the microtubule's minus end. It also functions in the movement of eukaryotic flagella and cilia. It consists of two heavy chains (about 500 kDa), three-four intermediate chains (about 70 kDa) and four light chains (about 50 kDa).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Summers, K.E. and Gibbons, I.R. Adenosine triphosphate-induced sliding of tubules in trypsin-treated flagella of sea-urchin sperm. Proc. Natl. Acad. Sci. USA 68 (1971) 3092-3096. [PMID: 5289252]
2. Gibbons, I.R. Dynein ATPases as microtubule motors. J. Biol. Chem. 263 (1988) 15837-15840. [PMID: 2972702]
3. Gee, M. and Vallee, R. The role of the dynein stalk in cytoplasmic and flagellar motility. Eur. Biophys. J. 27 (1998) 466-473. [PMID: 9760728]
Accepted name: plus-end-directed kinesin ATPase
Reaction: ATP + H2O + a kinesin associated with a microtubule at position n = ADP + phosphate a kinesin associated with a microtubule at position n+1 (toward the plus end)
Other name(s): kinesin
Systematic name: kinesin ATP phosphohydrolase (plus-end-directed)
Comments: Kinesins are a family of motor proteins that move unidirectionally along microtubules as they hydrolyse ATP. The enzymes described here move towards the plus end of the microtubule, in contrast to EC 5.6.1.2, dynein ATPase and EC 5.6.1.4, minus-end-directed kinesin ATPase. They are involved in organelle movement in mitosis and meiosis, and also power vesicular trafficking toward the synapse in neurons. The motor domain, which contains the ATP- and microtubule-binding activities, is located at the N-terminus while the C-terminus links to the cargo being transported.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Vale, R.D., Reese, T.S. and Sheetz, M.P. Identification of a novel force-generating protein, kinesin, in microtubule-based motility. Cell 42 (1985) 39-50. [PMID: 3926325]
2. Kull, F.J., Sablin, E.P., Lau, R., Fletterick, R.J. and Vale, R.D. Crystal structure of the kinesin motor domain reveals a structural similarity to myosin. Nature 380 (1996) 550-555. [PMID: 8606779]
3. Howard, J. Molecular motors: structural adaptations to cellular functions. Nature 389 (1997) 561-567. [PMID: 9335494]
4. Nakagawa, T., Tanaka, Y., Matsuoka, E., Kondo, S., Okada, Y., Noda, F., Kanai, Y. and Hirokawa, N. Identification and classification of 16 new kinesin superfamily (KIF) proteins in mouse genome. Proc. Natl. Acad. Sci. USA 94 (1997) 9654-9659. [PMID: 9275178]
5. Sindelar, C.V. and Downing, K.H. The beginning of kinesin’s force-generating cycle visualized at 9-Å resolution. J. Cell Biol. 177 (2007) 377-385. [PMID: 17470637]
6. Wang, W., Cao, L., Wang, C., Gigant, B. and Knossow, M. Kinesin, 30 years later: Recent insights from structural studies. Protein Sci. 24 (2015) 1047-1056. [PMID: 25975756]
Accepted name: minus-end-directed kinesin ATPase
Reaction: ATP + H2O + a kinesin associated with a microtubule at position n = ADP + phosphate + a kinesin associated with a microtubule at position n-1 (toward the minus end)
Other name(s): non-claret disjunctional; ncd (gene name)
Systematic name: kinesin ATP phosphohydrolase (minus-end-directed)
Comments: Kinesins are a family of motor proteins that move unidirectionally along microtubules as they hydrolyse ATP and are involved in organelle movement. This enzyme is similar to EC 5.6.1.3, plus-end-directed kinesin ATPase, but the organization of the different domains differs, resulting in movement in the opposite direction along the microtubules.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. McDonald, H.B., Stewart, R.J. and Goldstein, L.S. The kinesin-like ncd protein of Drosophila is a minus end-directed microtubule motor. Cell 63 (1990) 1159-1165. [PMID: 2261638]
2. Chandra, R., Salmon, E.D., Erickson, H.P., Lockhart, A. and Endow, S.A. Structural and functional domains of the Drosophila ncd microtubule motor protein. J. Biol. Chem 268 (1993) 9005-9013. [PMID: 8473343]
3. Lockhart, A. and Cross, R.A. Origins of reversed directionality in the ncd molecular motor. EMBO J. 13 (1994) 751-757. [PMID: 8112290]
4. Henningsen, U. and Schliwa, M. Reversal in the direction of movement of a molecular motor. Nature 389 (1997) 93-96. [PMID: 9288974]
5. Sablin, E.P., CASe, R.B., Dai, S.C., Hart, C.L., Ruby, A., Vale, R.D. and Fletterick, R.J. Direction determination in the minus-end-directed kinesin motor ncd. Nature 395 (1998) 813-816. [PMID: 9796817]
Accepted name: proteasome ATPase
Reaction: ATP + H2O + polypeptide = ADP + phosphate + unfolded polypeptide
Systematic name: ATP phosphohydrolase (polypeptide-degrading)
Comments: Belongs to the AAA-type superfamily and, like EC 5.6.1.4 (minus-end-directed kinesin ATPase), is involved in channel gating and polypeptide unfolding before proteolysis in the proteasome. Six ATPase subunits are present in the regulatory particle (RP) of 26S proteasome.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Rivett, A.J., Mason, G.G., Murray, R.Z. and Reidlinger, J. Regulation of proteasome structure and function. Mol. Biol. Rep. 24 (1997) 99-102. [PMID: 9228289]
2. Mason, G.G., Murray, R.Z., Pappin, D. and Rivett, A.J. Phosphorylation of ATPase subunits of the 26S proteasome. FEBS Lett. 430 (1998) 269-274. [PMID: 9688553]
Accepted name: channel-conductance-controlling ATPase
Reaction: ATP + H2O + closed Cl- channel = ADP + phosphate + open Cl- channel
Other name(s): cystic fibrosis transmembrane conductance regulator; CFTR (gene name)
Systematic name: ATP phosphohydrolase (channel-conductance-controlling)
Comments: ABC-type (ATP-binding cassette-type) ATPase, characterized by the presence of two similar ATP-binding domains. The enzyme is found in animals, and in humans its absence brings about cystic fibrosis. Unlike most of the ABC transporters, chloride pumping is not directly coupled to ATP hydrolysis. Instead, the passive flow of anions through the channel is gated by cycles of ATP binding and hydrolysis by the ATP-binding domains. The enzyme is also involved in the functioning of other transmembrane channels.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Chen, M. and Zhang, J.T. Membrane insertion, processing, and topology of cystic fibrosis transmembrane conductance regulator (CFTR) in microsomal membranes. Mol. Membr. Biol. 13 (1996) 33-40. [PMID: 9147660]
2. Tusnady, G.E., Bakos, E., Varadi, A. and Sarkadi, B. Membrane topology distinguishes a subfamily of the ATP-binding cassette (ABC) transporters. FEBS Lett. 402 (1997) 1-3. [PMID: 9013845]
3. Sheppard, D.N. and Welsh, M.J. Structure and function of the CFTR chloride channel. Physiol. Rev. 79 (1999) S23-S45. [PMID: 9922375]
4. Hwang, T.C. and Sheppard, D.N. Gating of the CFTR Cl- channel by ATP-driven nucleotide-binding domain dimerisation. J. Physiol. 587 (2009) 2151-2161. [PMID: 19332488]
Accepted name: chaperonin ATPase
Reaction: ATP + H2O + an unfolded polypeptide = ADP + phosphate + a folded polypeptide
Other name(s): chaperonin
Systematic name: ATP phosphohydrolase (polypeptide-unfolding)
Comments: Multisubunit proteins with 2x7 (Type I, in most cells) or 2x8 (Type II, in Archaea) ATP-binding sites involved in maintaining an unfolded polypeptide structure before folding or entry into mitochondria and chloroplasts. Molecular masses of subunits ranges from 10-90 kDa. They are a subclass of molecular chaperones that are related to EC 5.6.1.5 (proteasome ATPase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Hemmingsen, S.M., Woolford, C., van der Vies, S.M., Tilly, K., Dennis, D.T., Georgopoulos, G.C., Hendrix, R.W. and Ellis, R.J. Homologous plant and bacterial proteins: chaperone oligomeric protein assembly. Nature 333 (1988) 330-334. [PMID: 2897629]
2. Lubber, T.H., Donaldson, G.K., Viitanen, P.V. and Gatenby, A.A. Several proteins imported into chloroplasts form stable complexes with the GroEL-related chloroplast molecular chaperone. Plant Cell 1 (1989) 1223-1230. [PMID: 2577724]
3. Ellis, R.J. (Ed.), The Chaperonins, Academic Press, San Diego, 1996.
4. Ranson, N.A., White, H.E. and Saibil, H.R. Chaperonins. Biochem. J. 333 (1998) 233-242. [PMID: 9657960]
Accepted name: myosin ATPase
Reaction: ATP + H2O + myosin bound to actin filament at position n = ADP + phosphate + myosin bound to actin filament at position n+1
Systematic name: ATP phosphohydrolase (actin-translocating)
Comments: Proteins of the contractile apparatus of muscle and nonmuscle cells; myosin molecule consists of two heavy chains (about 200 kDa) and two pairs of light chains (15-27 kDa). The head region of the heavy chain contains actin- and ATP-binding sites. ATP hydrolysis provides energy for actomyosin contraction.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Rayment, I. The structural basis of myosin ATPase activity. J. Biol. Chem. 271 (1996) 15850-15853. [PMID: 8663496]
2. Hasson, T. and Mooseker, M.S. Vertebrate unconventional myosins. J. Biol. Chem. 271 (1996) 16431-16434. [PMID: 8690736]
3. Murphy, C.T. and Spudich, J.A. The sequence of the myosin 50-20K loop affects myosin's affinity for actin throughout the actin-myosin ATPase cycle and its maximum ATPase activity. Biochemistry 38 (1999) 3785-3792. [PMID: 10090768]
Accepted name: (R)-2-hydroxyacyl-CoA dehydratase activating ATPase
Reaction: 2 ATP + a reduced flavodoxin + an inactive (R)-2-hydroxyacyl-CoA dehydratase + 2 H2O = 2 ADP + 2 phosphate + a flavodoxin semiquinone + an active (R)-2-hydroxyacyl-CoA dehydratase
Other name(s): archerase; (R)-2-hydroxyacyl-CoA dehydratase activator; (R)-2-hydroxyacyl-CoA dehydratase activase; fldI (gene name); hgdC (gene name); hadI (gene name); lcdC (gene name)
Systematic name: reduced flavodoxin:(R)-2-hydroxyacyl-CoA dehydratase electron transferase (ATP-hydrolyzing)
Comments: Members of the (R)-2-hydroxyacyl-CoA dehydratase family (including EC 4.2.1.54, lactoyl-CoA dehydratase, EC 4.2.1.157, (R)-2-hydroxyisocaproyl-CoA dehydratase, EC 4.2.1.167, (R)-2-hydroxyglutaryl-CoA dehydratase and EC 4.2.1.175, (R)-3-(aryl)lactoyl-CoA dehydratase) are two-component systems composed of an activator component and a dehydratase component. The activator is an extremely oxygen-sensitive homodimer with one [4Fe-4S]cluster bound at the dimer interface. Before it can catalyse the dehydration reaction, the dehydratase requires one high-energy electron that is used to transiently reduce the electrophilic thiol ester carbonyl to a nucleophilic ketyl radical anion, facilitating the elimination of the hydroxyl group. The activator, which has been named archerase because its open position resembles an archer shooting arrows, binds two ADP molecules. Upon the reduction of its [4Fe-4S]cluster by a single electron, delivered by a dedicated flavodoxin or a clostridial ferredoxin, the two ADP molecules exchange for two ATP molecules, resulting in a large conformational change. The change allows the activator to bind to the dehydratase component and transfer the electron to it, activating it. During this event the two ATP molecules are hydrolysed and the activator returns to its resting state. Since the electron is regenerated at the end of each reaction cycle of the dehydratase, the activation is required only once, before the first reaction takes place.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Bendrat, K., Müller, U., Klees, A.G. and Buckel, W. Identification of the gene encoding the activator of (R)-2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans by gene expression in Escherichia coli. FEBS Lett. 329 (1993) 329-331. [PMID: 8365476]
2. Müller, U. and Buckel, W. Activation of (R)-2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans. Eur. J. Biochem. 230 (1995) 698-704. [PMID: 7607244]
3. Locher, K.P., Hans, M., Yeh, A.P., Schmid, B., Buckel, W. and Rees, D.C. Crystal structure of the Acidaminococcus fermentans 2-hydroxyglutaryl-CoA dehydratase component A. J. Mol. Biol. 307 (2001) 297-308. [PMID: 11243821]
4. Dickert, S., Pierik, A.J. and Buckel, W. Molecular characterization of phenyllactate dehydratase and its initiator from Clostridium sporogenes. Mol. Microbiol. 44 (2002) 49-60. [PMID: 11967068]
5. Thamer, W., Cirpus, I., Hans, M., Pierik, A.J., Selmer, T., Bill, E., Linder, D. and Buckel, W. A two [4Fe-4S]-cluster-containing ferredoxin as an alternative electron donor for 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans. Arch. Microbiol. 179 (2003) 197-204. [PMID: 12610725]
6. Kim, J., Hetzel, M., Boiangiu, C.D. and Buckel, W. Dehydration of (R)-2-Hydroxyacyl-CoA to enoyl-CoA in the fermentation of α-amino acids by anaerobic bacteria. FEMS Microbiol. Rev. 28 (2004) 455-468. [PMID: 15374661]
7. Kim, J., Darley, D. and Buckel, W. 2-Hydroxyisocaproyl-CoA dehydratase and its activator from Clostridium difficile. FEBS J. 272 (2005) 550-561. [PMID: 15654892]
8. Kim, J., Darley, D.J., Buckel, W. and Pierik, A.J. An allylic ketyl radical intermediate in clostridial amino-acid fermentation. Nature 452 (2008) 239-242. [PMID: 18337824]
9. Knauer, S.H., Buckel, W. and Dobbek, H. On the ATP-dependent activation of the radical enzyme (R)-2-hydroxyisocaproyl-CoA dehydratase. Biochemistry 51 (2012) 6609-6622. [PMID: 22827463]
EC 5.6.2.1 DNA topoisomerase
EC 5.6.2.2 DNA topoisomerase (ATP-hydrolysing)
EC 5.6.2.3 DNA 5′-3′ helicase
EC 5.6.2.4 DNA 3′-5′ helicase
EC 5.6.2.5 RNA 5′-3′ helicase
EC 5.6.2.6 RNA 3′-5′ helicase
EC 5.6.2.7 DEAD-box RNA helicase
Accepted name: DNA topoisomerase
Reaction: ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
Other name(s): type I DNA topoisomerase; untwisting enzyme; relaxing enzyme; nicking-closing enzyme; swivelase; ω-protein; deoxyribonucleate topoisomerase; topoisomerase
Systematic name: DNA topoisomerase
Comments: These enzymes bring about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences, cf. EC 5.6.2.2 DNA topoisomerase (ATP-hydrolysing).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Gellert, M. DNA topoisomerases. Annu. Rev. Biochem. 50 (1981) 879-910. [PMID: 6267993]
Accepted name: DNA topoisomerase (ATP-hydrolysing)
Reaction: ATP-dependent breakage, passage and rejoining of double-stranded DNA
Other name(s): type II DNA topoisomerase; DNA-gyrase; deoxyribonucleate topoisomerase; deoxyribonucleic topoisomerase; topoisomerase; DNA topoisomerase II
Systematic name: DNA topoisomerase (ATP-hydrolysing)
Comments: The enzyme can introduce negative superhelical turns into double-stranded circular DNA. One unit has nicking-closing activity, and another catalyses super-twisting and hydrolysis of ATP (cf. EC 5.6.2.1 DNA topoisomerase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Gellert, M. DNA topoisomerases. Annu. Rev. Biochem. 50 (1981) 879-910. [PMID: 6267993]
Accepted name: DNA 5'-3' helicase
Reaction: Couples ATP hydrolysis with the unwinding of duplex DNA at the replication fork by translocating in the 5'-3' direction. This creates two antiparallel DNA single strands (ssDNA). The leading ssDNA polymer is the template for DNA polymerase III holoenzyme which synthesizes a continuous strand.
Other name(s): DnaB helicase; replication fork helicase; 5' to 3' DNA helicase; BACH1 helicase; BcMCM; BLM protein; BRCA1-associated C-terminal helicase; CeWRN-1; Dbp9p; DNA helicase A; DNA helicase E; DNA helicase II; DNA helicase III; DNA helicase VI; dnaB (gene name); DnaB helicase E1; helicase HDH IV; Hel E; helicase DnaB; helicase domain of bacteriophage T7 gene 4 protein helicase; PcrA helicase; hHcsA; Hmi1p; hPif1; MCM helicase; MCM protein; MPH1; PcrA; PfDH A; Pfh1p; PIF1; replicative DNA helicase
Systematic name: DNA 5'-3' helicase (ATP-hydrolysing)
Comments: The activity is stimulated by DNA polymerase III. As the lagging ssDNA is created, it becomes coated with S Single-Stranded DNA Binding protein (SSB). Once every 500-2000 nucleotides, primase is stimulated by DnaB helicase to synthesize a primer at the replication fork. This primer is elongated by the lagging strand half of DNA polymerase III holoenzyme.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Lohman, T.M. Helicase-catalyzed DNA unwinding. J. Biol. Chem. 268 (1993) 2269-2272. [PMID: 8381400]
2. Jezewska, M.J. and Bujalowski, W. Global conformational transitions in Escherichia coli primary replicative helicase DnaB protein induced by ATP, ADP, and single-stranded DNA binding. Multiple conformational states of the helicase hexamer. J. Biol. Chem. 271 (1996) 4261-4265. [PMID: 8626772]
3. Ivessa, A.S., Zhou, J.Q., Schulz, V.P., Monson, E.K. and Zakian, V.A. Saccharomyces Rrm3p, a 5' to 3' DNA helicase that promotes replication fork progression through telomeric and subtelomeric DNA. Genes Dev. 16 (2002) 1383-1396. [PMID: 12050116]
4. Zhou, J.Q., Qi, H., Schulz, V.P., Mateyak, M.K., Monson, E.K. and Zakian, V.A. Schizosaccharomyces pombe pfh1+ encodes an essential 5' to 3' DNA helicase that is a member of the PIF1 subfamily of DNA helicases. Mol. Biol. Cell 13 (2002) 2180-2191. [PMID: 12058079]
5. Ivanov, K.A. and Ziebuhr, J. Human coronavirus 229E nonstructural protein 13: characterization of duplex-unwinding, nucleoside triphosphatase, and RNA 5'-triphosphatase activities. J. Virol. 78 (2004) 7833-7838. [PMID: 15220459]
6. Toseland, C.P. and Webb, M.R. ATPase mechanism of the 5'-3' DNA helicase, RecD2: evidence for a pre-hydrolysis conformation change. J. Biol. Chem. 288 (2013) 25183-25193. [PMID: 23839989]
Accepted name: DNA 3'-5' helicase
Reaction: Couples ATP hydrolysis with the unwinding of duplex DNA by translocating in the 3'-5' direction.
Other name(s): uvrD (gene name); rep (gene name); RECQ (gene name); MER3 (gene name); Holliday junction DNA helicase
Systematic name: DNA 3'-5' helicase (ATP-hydrolysing)
Comments: Helicases are motor proteins that can transiently catalyse the unwinding of energetically stable duplex DNA or RNA molecules by using ATP hydrolysis as the source of energy (although other nucleoside triphosphates can replace ATP in some cases). DNA helicases unwind duplex DNA and are involved in replication, repair, recombination, transcription, pre-rRNA processing, and translation initiation. Mechanistically, DNA helicases are divided into those that can translocate in the 3'-5' direction and those that translocate in the 5'-3' direction with respect to the strand on which they initially bind. This entry describes a number of DNA helicases that translocate in the 3'-5' direction. Many of the enzymes require a 3' single-stranded DNA tail. The Rep protein is a component of the bacterial replisome, providing a replication fork-specific motor. The UvrD enzyme, found in Gram-negative bacteria, is involved in maintenance of chromosomal integrity. The RecQ proteins are a family of eukaryotic helicases that are involved in DNA replication, transcription and repair. The Mer3 helicase, found in fungi and plants, is required for crossover formation during meiosis. cf. EC 5.6.2.3, DNA 5'-3' helicase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Takahashi, S., Hours, C., Chu, A. and Denhardt, D.T. The rep mutation. VI. Purification and properties of the Escherichia coli rep protein, DNA helicase III. Can. J. Biochem. 57 (1979) 855-866. [PMID: 383240]
2. Nakagawa, T., Flores-Rozas, H. and Kolodner, R.D. The MER3 helicase involved in meiotic crossing over is stimulated by single-stranded DNA-binding proteins and unwinds DNA in the 3' to 5' direction. J. Biol. Chem. 276 (2001) 31487-31493. [PMID: 11376001]
3. Ozsoy, A.Z., Sekelsky, J.J. and Matson, S.W. Biochemical characterization of the small isoform of Drosophila melanogaster RECQ5 helicase. Nucleic Acids Res. 29 (2001) 2986-2993. [PMID: 11452023]
4. Curti, E., Smerdon, S.J. and Davis, E.O. Characterization of the helicase activity and substrate specificity of Mycobacterium tuberculosis UvrD. J. Bacteriol. 189 (2007) 1542-1555. [PMID: 17158674]
Accepted name: RNA 5'-3' helicase
Reaction: n ATP + n H2O + wound RNA = n ADP + n phosphate + unwound RNA
Other name(s): corona virus helicase nsP13; MOV10; Moloney leukemia virus 10; UPF1; sen1+
Systematic name: RNA 5'-3' helicase (ATP-hydrolysing)
Comments: RNA helicases, which participate in nearly all aspects of RNA metabolism, utilize the energy from ATP hydrolysis to unwind RNA. The engine core of helicases is usually made of a pair of RecA-like domains that form an NTP binding cleft at their interface. Changes in the chemical state of the NTP binding cleft (binding of the NTP or its hydrolysis products) alter the relative positions of the RecA-like domains and nucleic acid-binding domains, creating structural motions that disrupt the pairing of the nucleic acid, causing separation and unwinding. Most RNA helicases utilize a mechanism known as canonical duplex unwinding, in which the helicase binds to a single stranded region adjacent to the duplex and then translocates along the bound strand with defined directionality, displacing the complementary strand. Most of these helicases proceed 3' to 5' (type A polarity - cf. EC 5.6.2.6, RNA 3'-5' helicase), but some proceed 5' to 3' (type B polarity), and some are able to catalyse unwinding in either direction [1,4]. Most canonically operating helicases require substrates with single stranded regions in a defined orientation (polarity) with respect to the duplex. A different class of RNA helicases, EC 5.6.2.7, DEAD-box RNA helicase, use a different mechanism and unwind short stretches of RNA with no translocation.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Rozen, F., Edery, I., Meerovitch, K., Dever, T.E., Merrick, W.C. and Sonenberg, N. Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F. Mol. Cell Biol. 10 (1990) 1134-1144. [PMID: 2304461]
2. Kim, H.D., Choe, J. and Seo, Y.S. The sen1(+) gene of Schizosaccharomyces pombe, a homologue of budding yeast SEN1, encodes an RNA and DNA helicase. Biochemistry 38 (1999) 14697-14710. [PMID: 10545196]
3. Bhattacharya, A., Czaplinski, K., Trifillis, P., He, F., Jacobson, A. and Peltz, S.W. Characterization of the biochemical properties of the human Upf1 gene product that is involved in nonsense-mediated mRNA decay. RNA 6 (2000) 1226-1235. [PMID: 10999600]
4. Lee, C.G. RH70, a bidirectional RNA helicase, co-purifies with U1snRNP. J. Biol. Chem. 277 (2002) 39679-39683. [PMID: 12193588]
5. Gregersen, L.H., Schueler, M., Munschauer, M., Mastrobuoni, G., Chen, W., Kempa, S., Dieterich, C. and Landthaler, M. MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA target degradation by translocation along 3' UTRs. Mol. Cell 54 (2014) 573-585. [PMID: 24726324]
6. Jang, K.J., Jeong, S., Kang, D.Y., Sp, N., Yang, Y.M. and Kim, D.E. A high ATP concentration enhances the cooperative translocation of the SARS coronavirus helicase nsP13 in the unwinding of duplex RNA. Sci. Rep. 10 (2020) 4481. [PMID: 32161317]
Accepted name: RNA 3'-5' helicase
Reaction: n ATP + n H2O + wound RNA = n ADP + n phosphate + unwound RNA
Other name(s): DEAH/RHA protein; DEAH-box protein 2; Prp22p; DHX8; DHX36; CSFV NS3 helicase; nonstructural protein 3 helicase; KOKV helicase; Kokobera virus helicase; hepatitis C virus NS3 protein; DExH protein; MTR4; SKI2; BRR2; SUV3; Rig-I; retinoic-acid-inducible gene I; DbpA
Systematic name: RNA 3'-5' helicase (ATP-hydrolysing)
Comments: RNA helicases, which participate in nearly all aspects of RNA metabolism, utilize the energy from ATP hydrolysis to unwind RNA. The engine core of helicases is usually made of a pair of RecA-like domains that form an NTP binding cleft at their interface. Changes in the chemical state of the NTP binding cleft (binding of the NTP or its hydrolysis products) alter the relative positions of the RecA-like domains and nucleic acid-binding domains, creating structural motions that disrupt the pairing of the nucleic acid, causing separation and unwinding. Most RNA helicases utilize a mechanism known as canonical duplex unwinding, in which the helicase binds to a single stranded region adjacent to the duplex and then translocates along the bound strand with defined directionality, displacing the complementary strand. Most of these helicases proceed 3' to 5' (type A polarity), but some proceed 5' to 3' (type B polarity - cf. EC 5.6.2.5, RNA 5'-3' helicase), and some are able to catalyse unwinding in either direction [1,3]. Most canonically operating helicases require substrates with single stranded regions in a defined orientation (polarity) with respect to the duplex. A different class of RNA helicases, EC 5.6.2.7, DEAD-box RNA helicase, use a different mechanism and unwind short stretches of RNA with no translocation.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Rozen, F., Edery, I., Meerovitch, K., Dever, T.E., Merrick, W.C. and Sonenberg, N. Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F. Mol. Cell Biol. 10 (1990) 1134-1144. [PMID: 2304461]
2. Shuman, S. Vaccinia virus RNA helicase. Directionality and substrate specificity. J. Biol. Chem. 268 (1993) 11798-11802. [PMID: 8505308]
3. Lee, C.G. RH70, a bidirectional RNA helicase, co-purifies with U1snRNP. J. Biol. Chem. 277 (2002) 39679-39683. [PMID: 12193588]
4. Zhang, S. and Grosse, F. Multiple functions of nuclear DNA helicase II (RNA helicase A) in nucleic acid metabolism. Acta Biochim Biophys Sin (Shanghai) 36 (2004) 177-183. [PMID: 15202501]
5. Diges, C.M. and Uhlenbeck, O.C. Escherichia coli DbpA is a 3' → 5' RNA helicase. Biochemistry 44 (2005) 7903-7911. [PMID: 15910005]
6. Frick, D.N. The hepatitis C virus NS3 protein: a model RNA helicase and potential drug target. Curr. Issues Mol. Biol. 9 (2007) 1-20. [PMID: 17263143]
7. Schwer, B. A conformational rearrangement in the spliceosome sets the stage for Prp22-dependent mRNA release. Mol. Cell 30 (2008) 743-754. [PMID: 18570877]
8. Takahasi, K., Yoneyama, M., Nishihori, T., Hirai, R., Kumeta, H., Narita, R., Gale, M., Jr., Inagaki, F. and Fujita, T. Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses. Mol. Cell 29 (2008) 428-440. [PMID: 18242112]
9. Wang, X., Jia, H., Jankowsky, E. and Anderson, J.T. Degradation of hypomodified tRNA(iMet) in vivo involves RNA-dependent ATPase activity of the DExH helicase Mtr4p. RNA 14 (2008) 107-116. [PMID: 18000032]
10. Wen, G., Xue, J., Shen, Y., Zhang, C. and Pan, Z. Characterization of classical swine fever virus (CSFV) nonstructural protein 3 (NS3) helicase activity and its modulation by CSFV RNA-dependent RNA polymerase. Virus Res. 141 (2009) 63-70. [PMID: 19185595]
Accepted name: DEAD-box RNA helicase
Reaction: ATP + H2O + wound RNA = ADP + phosphate + unwound RNA
Other name(s): Dbp2; DDX3; DDX4; DDX5; DDX17; DDX3Y; RM62; hDEAD1; RNA helicase Hera; DED1
Systematic name: RNA helicase (non-translocating)
Comments: RNA helicases, which participate in nearly all aspects of RNA metabolism, utilize the energy from ATP hydrolysis to unwind RNA. The engine core of helicases is usually made of a pair of RecA-like domains that form an NTP binding cleft at their interface. Changes in the chemical state of the NTP binding cleft (binding of the NTP or its hydrolysis products) alter the relative positions of the RecA-like domains and nucleic acid-binding domains, creating structural motions that disrupt the pairing of the nucleic acid, causing separation and unwinding. While most RNA helicases utilize a mechanism known as canonical duplex unwinding and translocate along the RNA (cf. EC 5.6.2.5, RNA 5'-3' helicase and EC 5.6.2.6, RNA 3'-5' helicase), DEAD-box RNA helicases differ by unwinding RNA via the local strand separation mechanism, which does not involve translocation. These helicases load directly on the duplex region, aided by single stranded or structured nucleic acid regions. Upon loading, the DEAD-box protein locally opens the duplex strands. This step requires binding of ATP, which is not hydrolysed. The local helix opening causes the remaining basepairs to dissociate without further action from the enzyme. Unwinding occurs without apparent polarity, and is limited to relatively short distances. ATP hydrolysis is required for release of the DEAD-box protein from the RNA. The name originates from the sequence D-E-A-D, which is found in Motif II of these proteins.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Linder, P., Lasko, P.F., Ashburner, M., Leroy, P., Nielsen, P.J., Nishi, K., Schnier, J. and Slonimski, P.P. Birth of the D-E-A-D box. Nature 337 (1989) 121-122. [PMID: 2563148]
2. Tang, P.Z., Tsai-Morris, C.H. and Dufau, M.L. A novel gonadotropin-regulated testicular RNA helicase. A new member of the dead-box family. J. Biol. Chem. 274 (1999) 37932-37940. [PMID: 10608860]
3. Rossler, O.G., Straka, A. and Stahl, H. Rearrangement of structured RNA via branch migration structures catalysed by the highly related DEAD-box proteins p68 and p72. Nucleic Acids Res. 29 (2001) 2088-2096. [PMID: 11353078]
4. Bizebard, T., Ferlenghi, I., Iost, I. and Dreyfus, M. Studies on three E. coli DEAD-box helicases point to an unwinding mechanism different from that of model DNA helicases. Biochemistry 43 (2004) 7857-7866. [PMID: 15196029]
5. Garbelli, A., Beermann, S., Di Cicco, G., Dietrich, U. and Maga, G. A motif unique to the human DEAD-box protein DDX3 is important for nucleic acid binding, ATP hydrolysis, RNA/DNA unwinding and HIV-1 replication. PLoS One 6 (2011) e19810. [PMID: 21589879]
6. Jarmoskaite, I. and Russell, R. DEAD-box proteins as RNA helicases and chaperones. Wiley Interdiscip Rev RNA 2 (2011) 135-152. [PMID: 21297876]
7. Linder, P. and Fuller-Pace, F.V. Looking back on the birth of DEAD-box RNA helicases. Biochim. Biophys Acta 1829 (2013) 750-755. [PMID: 23542735]
EC 5.99.1.4 2-hydroxychromene-2-carboxylate isomerase
Accepted name: thiocyanate isomerase
Reaction: benzyl isothiocyanate = benzyl thiocyanate
Other name(s): isothiocyanate isomerase
Systematic name: benzyl-thiocyanate isomerase
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9023-71-6
References:
1. Virtanen, A.I. On enzymic and chemical reactions in crushed plants. Arch. Biochem. Biophys. Suppl. 1 (1962) 200-208.
[EC 5.99.1.2 Transferred entry: DNA topoisomerase. Now EC 5.6.2.1, DNA topoisomerase(EC 5.99.1.2 created 1984, deleted 2018)]
[EC 5.99.1.3 Transferred entry: DNA topoisomerase (ATP-hydrolysing). Now EC 5.6.2.2, DNA topoisomerase (ATP-hydrolysing)(EC 5.99.1.3 created 1984, deleted 2018)]
Accepted name: 2-hydroxychromene-2-carboxylate isomerase
Reaction: 2-hydroxy-2H-chromene-2-carboxylate = (3E)-4-(2-hydroxyphenyl)-2-oxobut-3-enoate
For diagram of reaction, click here
Other name(s): HCCA isomerase; 2HC2CA isomerase; 2-hydroxychromene-2-carboxylic acid isomerase
Systematic name: 2-hydroxy-2H-chromene-2-carboxylate—(3E)-4-(2-hydroxyphenyl)-2-oxobut-3-enoate isomerase
Comments: This enzyme is involved in naphthalene degradation.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Ohmoto, T., Kinoshita, T., Moriyoshi, K., Sakai, K., Hamada, N. and Ohe, T. Purification and some properties of 2-hydroxychromene-2-carboxylate isomerase from naphthalenesulfonate-assimilating Pseudomonas sp. TA-2. J. Biochem. 124 (1998) 591-597. [PMID: 9722670]
2. Keck, A., Conradt, D., Mahler, A., Stolz, A., Mattes, R. and Klein, J. Identification and functional analysis of the genes for naphthalenesulfonate catabolism by Sphingomonas xenophaga BN6. Microbiology 152 (2006) 1929-1940. [PMID: 16804169]
3. Eaton, R.W. Organization and evolution of naphthalene catabolic pathways: sequence of the DNA encoding 2-hydroxychromene-2-carboxylate isomerase and trans-o-hydroxybenzylidenepyruvate hydratase-aldolase from the NAH7 plasmid. J. Bacteriol. 176 (1994) 7757-7762. [PMID: 8002605]
4. Thompson, L.C., Ladner, J.E., Codreanu, S.G., Harp, J., Gilliland, G.L. and Armstrong, R.N. 2-Hydroxychromene-2-carboxylic acid isomerase: a kappa class glutathione transferase from Pseudomonas putida. Biochemistry 46 (2007) 6710-6722. [PMID: 17508726]