Mechanisms and structures of crotonase superfamily enzymes--how nature controls enolate and oxyanion reactivity.

Journal article

Structural and mechanistic studies on the crotonase superfamily (CS) are reviewed with the aim of illustrating how a conserved structural platform can enable catalysis of a very wide range of reactions. Many CS reactions have precedent in the 'carbonyl' chemistry of organic synthesis; they include alkene hydration/isomerization, aryl-halide dehalogenation, (de)carboxylation, CoA ester and peptide hydrolysis, fragmentation of beta-diketones and C-C bond formation, cleavage and oxidation. CS enzymes possess a canonical fold formed from repeated betabetaalpha units that assemble into two approximately perpendicular beta-sheets surrounded by alpha-helices. CS enzymes often, although not exclusively, oligomerize as trimers or dimers of trimers. Two conserved backbone NH groups in CS active sites form an oxyanion 'hole' that can stabilize enolate/oxyanion intermediates. The range and efficiency of known CS-catalyzed reactions coupled to their common structural platforms suggest that CS variants may have widespread utility in biocatalysis.

Authors: Hamed, R; Batchelar, E; Clifton, I; Schofield, C

• Publication status: Published
• Journal: Cellular and molecular life sciences : CMLS
• Volume: 65
• Issue: 16
• Pages: 2507-2527
• Publication date: 2008-08-01
• DOI: 10.1007/s00018-008-8082-6
• EISSN: 1420-9071
• ISSN: 1420-682X
• Language: English
• Keywords: Binding Sites; Protein Structure, Quaternary; Animals; Carboxylic Acids; Humans; Enoyl-CoA Hydratase; Molecular Sequence Data; Protein Structure, Secondary; Nature; Amino Acid Sequence