Enoyl-CoA hydratase/isomerase family
Identifiers
SymbolECH
PfamPF00378
InterProIPR001753
PROSITEPDOC00150
SCOP21dub / SCOPe / SUPFAM
CDDcd06558
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1dubA:48-214 2dubE:48-214 1ey3B:48-214

1mj3A:48-214 1hzdD:90-259 1wdmA:18-190 1wdkB:18-190 1wdlB:18-190 1uiyA:10-180 2f6qB:116-287 1q52B:48-235 1q51B:48-235 1rjnA:48-235 1rjmA:48-235 1dciA:67-247 1wz8B:22-191 2a81A:11-180 2a7kF:11-180 1ef8B:15-183 1ef9A:15-183 1pjhA:20-200 1k39B:20-200 1hnoA:20-200 1hnuA:20-200 2fbmA:295-467 1szoC:27-195 1o8uD:27-195

1xx4A:45-215 1sg4C:58-228

The crotonase family comprises mechanistically diverse proteins that share a conserved trimeric quaternary structure (sometimes a hexamer consisting of a dimer of trimers), the core of which consists of 4 turns of a (beta/beta/alpha)n superhelix.

Some enzymes in the superfamily have been shown to display dehalogenase, hydratase, and isomerase activities, while others have been implicated in carbon-carbon bond formation and cleavage as well as the hydrolysis of thioesters.[1] However, these different enzymes share the need to stabilize an enolate anion intermediate derived from an acyl-CoA substrate. This is accomplished by two structurally conserved peptidic NH groups that provide hydrogen bonds to the carbonyl moieties of the acyl-CoA substrates and form an "oxyanion hole". The CoA thioester derivatives bind in a characteristic hooked shape and a conserved tunnel binds the pantetheine group of CoA, which links the 3'-phosphate ADP binding site to the site of reaction.[2] Enzymes in the crotonase superfamily include:

  • Enoyl-CoA hydratase (crotonase; EC 4.2.1.17), which catalyses the hydratation of 2-trans-enoyl-CoA into 3-hydroxyacyl-CoA.[3]
  • 3-2trans-enoyl-CoA isomerase (or dodecenoyl-CoA isomerise; EC 5.3.3.8), which shifts the 3-double bond of the intermediates of unsaturated fatty acid oxidation to the 2-trans position.[4]
  • 3-hydroxybutyryl-CoA dehydrogenase (crotonase; EC 4.2.1.55), a bacterial enzyme involved in the butyrate/butanol-producing pathway.
  • 4-Chlorobenzoyl-CoA dehalogenase (EC 3.8.1.6), a Pseudomonas enzyme which catalyses the conversion of 4-chlorobenzoate-CoA to 4-hydroxybenzoate-CoA.[5]
  • Dienoyl-CoA isomerase, which catalyses the isomerisation of 3-trans,5-cis-dienoyl-CoA to 2-trans,4-trans-dienoyl-CoA.[6]
  • Naphthoate synthase (MenB, or DHNA synthetase; EC 4.1.3.36), a bacterial enzyme involved in the biosynthesis of menaquinone (vitamin K2).[7]
  • Carnitine racemase (gene caiD), which catalyses the reversible conversion of crotonobetaine to L-carnitine in Escherichia coli.[8]
  • Methylmalonyl CoA decarboxylase (MMCD; EC 4.1.1.41), which has a hexameric structure (dimer of trimers).[9]
  • Carboxymethylproline synthase (CarB), which is involved in carbapenem biosynthesis.[10]
  • 6-oxo camphor hydrolase, which catalyses the desymmetrization of bicyclic beta-diketones to optically active keto acids.[11]
  • The alpha subunit of fatty acid oxidation complex, a multi-enzyme complex that catalyses the last three reactions in the fatty acid beta-oxidation cycle.[12]
  • AUH protein, a bifunctional RNA-binding homologue of enoyl-CoA hydratase.[13]

Human proteins containing this domain

AUH; CDY2B; CDYL; CDYL2; DCI; ECH1; ECHDC1; ECHDC2; ECHDC3; ECHS1; EHHADH; HADHA; HCA64; HIBCH; PECI;

References

  1. ↑ Gerlt JA, Benning MM, Holden HM, Haller T (2001). "The crotonase superfamily: divergently related enzymes that catalyze different reactions involving acyl coenzyme a thioesters". Acc. Chem. Res. 34 (2): 145–57. doi:10.1021/ar000053l. PMID 11263873.
  2. ↑ Brzozowski AM, Leonard PM, Bennett JP, Whittingham JL, Grogan G (2007). "Structural characterization of a beta-diketone hydrolase from the cyanobacterium Anabaena sp. PCC 7120 in native and product-bound forms, a coenzyme A-independent member of the crotonase suprafamily". Biochemistry. 46 (1): 137–44. doi:10.1021/bi061900g. PMID 17198383.
  3. ↑ Wu J, Kisker C, Whitty A, Feng Y, Rudolph MJ, Bell AF, Hofstein HA, Parikh S, Tonge PJ (2002). "Stereoselectivity of enoyl-CoA hydratase results from preferential activation of one of two bound substrate conformers". Chem. Biol. 9 (11): 1247–55. doi:10.1016/S1074-5521(02)00263-6. PMID 12445775.
  4. ↑ Stoffel W, Muller-Newen G (1991). "Mitochondrial 3-2trans-Enoyl-CoA isomerase. Purification, cloning, expression, and mitochondrial import of the key enzyme of unsaturated fatty acid beta-oxidation". Biol. Chem. Hoppe-Seyler. 372 (8): 613–624. doi:10.1515/bchm3.1991.372.2.613. PMID 1958319.
  5. ↑ Dunaway-Mariano D, Benning MM, Wesenberg G, Holden HM, Taylor KL, Yang G, Liu R-Q, Xiang H (1996). "Structure of 4-chlorobenzoyl coenzyme A dehalogenase determined to 1.8 A resolution: an enzyme catalyst generated via adaptive mutation". Biochemistry. 35 (25): 8103–9. doi:10.1021/bi960768p. PMID 8679561.
  6. ↑ Hiltunen JK, Wierenga RK, Modis Y, Filppula SA, Novikov DK, Norledge B (1998). "The crystal structure of dienoyl-CoA isomerase at 1.5 A resolution reveals the importance of aspartate and glutamate sidechains for catalysis". Structure. 6 (8): 957–70. doi:10.1016/s0969-2126(98)00098-7. PMID 9739087.
  7. ↑ Baker EN, Johnston JM, Arcus VL (2005). "Structure of naphthoate synthase (MenB) from Mycobacterium tuberculosis in both native and product-bound forms". Acta Crystallogr. D. 61 (Pt 9): 1199–206. doi:10.1107/S0907444905017531. PMID 16131752.
  8. ↑ Kleber HP, Elssner T, Engemann C, Baumgart K (2001). "Involvement of coenzyme A esters and two new enzymes, an enoyl-CoA hydratase and a CoA-transferase, in the hydration of crotonobetaine to L-carnitine by Escherichia coli". Biochemistry. 40 (37): 11140–8. doi:10.1021/bi0108812. PMID 11551212.
  9. ↑ Gerlt JA, Benning MM, Holden HM, Haller T (2000). "New reactions in the crotonase superfamily: structure of methylmalonyl CoA decarboxylase from Escherichia coli". Biochemistry. 39 (16): 4630–9. doi:10.1021/bi9928896. PMID 10769118.
  10. ↑ Schofield CJ, McDonough MA, Sleeman MC, Sorensen JL, Batchelar ET (2005). "Structural and mechanistic studies on carboxymethylproline synthase (CarB), a unique member of the crotonase superfamily catalyzing the first step in carbapenem biosynthesis". J. Biol. Chem. 280 (41): 34956–65. doi:10.1074/jbc.M507196200. PMID 16096274.
  11. ↑ Leonard PM, Grogan G (2004). "Structure of 6-oxo camphor hydrolase H122A mutant bound to its natural product, (2S,4S)-alpha-campholinic acid: mutant structure suggests an atypical mode of transition state binding for a crotonase homolog". J. Biol. Chem. 279 (30): 31312–17. doi:10.1074/jbc.M403514200. PMID 15138275.
  12. ↑ Resibois-Gregoire A, Dourov N (1966). "Electron microscopic study of a case of cerebral glycogenosis". Acta Neuropathol. 6 (1): 70–9. doi:10.1007/BF00691083. PMID 5229654. S2CID 21331079.
  13. ↑ Nureki O, Fukai S, Yokoyama S, Muto Y, Kurimoto K (2001). "Crystal structure of human AUH protein, a single-stranded RNA binding homolog of enoyl-CoA hydratase". Structure. 9 (12): 1253–63. doi:10.1016/S0969-2126(01)00686-4. PMID 11738050.
This article incorporates text from the public domain Pfam and InterPro: IPR001753
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