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]