InterPro: IPR018376 Enoyl-CoA hydratase/isomerase, conserved site

The crotonase superfamily is comprised of 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 stabilise 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-hydroxbutyryl-CoA dehydratase (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 isomerise, 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 desymmetrisation of bicyclic beta-diketones to optically active keto acids [11].
• The alpha subunit of fatty 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].