Crotonase family
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
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