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. 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. 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.
  • 3-2trans-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.
  • 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.
  • Dienoyl-CoA isomerase, which catalyses the isomerisation of 3-trans,5-cis-dienoyl-CoA to 2-trans,4-trans-dienoyl-CoA.
  • Naphthoate synthase (MenB, or DHNA synthetase; EC 4.1.3.36), a bacterial enzyme involved in the biosynthesis of menaquinone (vitamin K2).
  • Carnitine racemase (gene caiD), which catalyses the reversible conversion of crotonobetaine to L-carnitine in Escherichia coli.
  • Methylmalonyl CoA decarboxylase (MMCD; EC 4.1.1.41), which has a hexameric structure (dimer of trimers).
  • Carboxymethylproline synthase (CarB), which is involved in carbapenem biosynthesis.
  • 6-oxo camphor hydrolase, which catalyses the desymmetrization of bicyclic beta-diketones to optically active keto acids.
  • 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.
  • AUH protein, a bifunctional RNA-binding homologue of enoyl-CoA hydratase.

Read more about Crotonase Family:  Human Proteins Containing This Domain

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