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

被引:98
作者
Hamed, R. B. [1 ]
Batchelar, E. T. [1 ]
Clifton, I. J. [1 ]
Schofield, C. J. [1 ]
机构
[1] Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England
基金
英国生物技术与生命科学研究理事会;
关键词
crotonase superfamily; oxyanion hole; enolate intermediates; coenzyme A; beta-oxidation; proteases;
D O I
10.1007/s00018-008-8082-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 beta beta alpha 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.
引用
收藏
页码:2507 / 2527
页数:21
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