Mechanisms and structures of crotonase superfamily enzymes--how nature controls enolate and oxyanion reactivity.
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.
Hamed
R B
RB
Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK.
Batchelar
E T
ET
Clifton
I J
IJ
Schofield
C J
CJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002264:Carboxylic Acids / Q000378:metabolism*; D004746:Enoyl-CoA Hydratase / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D019368:Nature; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary
D002264:Carboxylic Acids; D004746:Enoyl-CoA Hydratase