Relationships of human α/β hydrolase fold proteins and other organophosphate-interacting proteins
Relationships of human α/β hydrolase fold proteins and other organophosphate-interacting proteins
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DOI：
10.1016/j.cbi.2016.04.027
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发表时间：
2016-11-25
影响因子：
5.1
通讯作者：
Chatonnet, Arnaud
中科院分区：
文献类型：
--
作者：
Lenfant, Nicolas;Bourne, Yves;Chatonnet, Arnaud
有机磷酸盐(OPs)在自然界中存在，或被合成用作杀虫剂、阻燃剂、神经毒性战剂或药物(阿尔茨海默病和重症肌无力的胆碱能增强剂，或代谢性疾病的脂肪酶抑制剂)。由于乙酰胆碱酯酶在人类胆碱能神经传递中的中心作用，使用OPs的主要目的之一是通过活性中心的亲核丝氨酸残基的磷酸化来灭活该酶。然而，数以百计的丝氨酸水解酶在人类蛋白质组中表达，其中许多是OP内收的潜在靶点。在这篇综述中，我们首先将α/β水解酶折叠蛋白定位在已知与OP相互作用的不同折叠蛋白中，特别是不同的脂肪酶、多肽酶和水解OP的酶。其次，我们编译了人类α/β水解酶，并回顾了那些已被实验证明与OP相互作用的水解酶。在120个人a/b水解酶折叠蛋白中，102个具有与活性中心相容的GXSXG五肽中的丝氨酸，6个具有天冬氨酸或半胱氨酸作为活性中心亲核残基，12个明显缺乏活性中心。120个中的76个已经被实验证明可以结合OP。(C)2016爱思唯尔爱尔兰有限公司。保留所有权利。
Organophosphates (OPs) are either found in nature or synthetized for use as pesticides, flame retardants, neurotoxic warfare agents or drugs (cholinergic enhancers in Alzheimer's disease and myasthenia gravis, or inhibitors of lipases in metabolic diseases). Because of the central role of acetylcholinesterase cholinergic neurotransmission in humans, one of the main purposes for using OPs is inactivation of the enzyme by phosphorylation of the nucleophilic serine residue in the active center. However, hundreds of serine hydrolases are expressed in the human proteome, and many of them are potential targets for OP adduction. In this review, we first situate the alpha/beta hydrolase fold proteins among the distinctively folded proteins known to interact with OPs, in particular the different lipases, peptidases, and enzymes hydrolyzing OPs. Second, we compile the human alpha/beta hydrolases and review those that have been experimentally shown to interact with OPs. Among the 120 human a/b hydrolase fold proteins, 102 have a serine in the consensus GXSXG pentapeptide compatible with an active site, 6 have an aspartate or a cysteine as the active site nucleophile residue, and 12 evidently lack an active site. 76 of the 120 have been experimentally shown to bind an OP. (C) 2016 Elsevier Ireland Ltd. All rights reserved.