SEQUENCE SIMILARITY OF MAMMALIAN EPOXIDE HYDROLASES TO THE BACTERIAL HALOALKANE DEHALOGENASE AND OTHER RELATED PROTEINS - IMPLICATION FOR THE POTENTIAL CATALYTIC MECHANISM OF ENZYMATIC EPOXIDE HYDROLYSIS
SEQUENCE SIMILARITY OF MAMMALIAN EPOXIDE HYDROLASES TO THE BACTERIAL HALOALKANE DEHALOGENASE AND OTHER RELATED PROTEINS - IMPLICATION FOR THE POTENTIAL CATALYTIC MECHANISM OF ENZYMATIC EPOXIDE HYDROLYSIS
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DOI：
10.1016/0014-5793(94)80278-5
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发表时间：
1994-02-07
期刊：
影响因子：
3.5
通讯作者：
HAMMOCK, BD
中科院分区：
文献类型：
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作者：
ARAND, M;GRANT, DF;HAMMOCK, BD
微粒体和可溶性环氧化物水解酶的氨基酸序列的直接比较表面上表明，这些酶是无关的。然而，这两种蛋白质，共享显着的序列相似性的细菌卤代烷脱卤酶，已被证明属于碱性磷酸酶折叠酶家族。脱卤酶的催化机制已被详细阐明[Verschueren等（1993）Nature 363，693-698]，并通过酯中间体进行，其中底物与酶共价结合。从这些观察中，我们得出结论：（i）微粒体和可溶性环氧化物水解酶是远亲酶，它们与卤代烷脱卤酶和本文中指定的各种其他蛋白质一起从共同的祖先蛋白质进化而来，（ii）这些酶最可能属于α/β水解酶折叠家族，以及（iii）酶促环氧化物水解通过羟基酯中间体进行，这与目前有利的通过活化水对环氧化物的碱催化直接攻击相反。
Direct comparison of the amino acid sequences of microsomal and soluble epoxide hydrolase superficially indicates that these enzymes are unrelated. Both proteins, however, share significant sequence similarity to a bacterial haloalkane dehalogenase that has earlier been shown to belong to the alp hydrolase fold family of enzymes. The catalytic mechanism for the dehalogenase has been elucidated in detail [Verschueren et al. (1993) Nature 363, 693-698] and proceeds via an ester intermediate where the substrate is covalently bound to the enzyme. From these observations we conclude (i) that microsomal and soluble epoxide hydrolase are distantly related enzymes that have evolved from a common ancestral protein together with the haloalkane dehalogenase and a variety of other proteins specified in the present paper, (ii) that these enzymes most likely belong to the alpha/beta hydrolase fold family of enzymes and (iii) that the enzymatic epoxide hydrolysis proceeds via a hydroxy ester intermediate, in contrast to the presently favoured base-catalyzed direct attack of the epoxide by an activated water.