Sequence and structure of epoxide hydrolases: A systematic analysis
Sequence and structure of epoxide hydrolases: A systematic analysis
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DOI：
10.1002/prot.20013
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发表时间：
2004-06-01
影响因子：
2.9
通讯作者：
Pleiss, J
中科院分区：
文献类型：
--
作者：
Barth, S;Fischer, M;Pleiss, J
环氧化物水解酶 (EC 3.3.2.3) 是一种普遍存在的酶，可催化环氧化物水解成相应的邻位二醇。已鉴定或预测了 100 多种环氧化物水解酶 (EH)，并且有 3 种结构可用。尽管它们催化相同的化学反应，但序列相似性较低。为了识别保守区域，所有 EH 都进行了对齐。系统发育分析鉴定出12个同源家族，分为2个主要超家族：微粒体EH超家族，包括哺乳动物、昆虫、真菌和细菌EH同源家族，以及胞质EH超家族，包括哺乳动物、植物和细菌EH。细菌 EH 显示出高度的序列多样性。基于放射农杆菌 AD1（胞质 EH）、黑曲霉（微粒体 EH）、小家鼠（胞质 EH）三种已知结构的结构比较，以及 95 个 EH 的多序列比对和系统发育分析，对该酶家族的模块化结构进行了分析。尽管核心和帽结构域高度保守，但EH之间的结构差异仅限于两个环：连接核心和帽的NC环以及插入帽结构域的帽环。根据循环长度将 EH 分配到三个簇中的任意一个。通过使用这种分类，可以对所有 EH 的核心和帽区域、所有 EH 的 78% 和 89% 的 NC 环和帽环分别进行建模。代表性模型可从脂肪酶工程数据库获得，http://www.led.uni-stuttgart.de。 (C) 2004Wiley-Liss, Inc.
Epoxide hydrolases (EC 3.3.2.3) are ubiquitous enzymes that catalyze the hydrolysis of epoxides to the corresponding vicinal diols. More than 100 epoxide hydrolases (EH) have been identified or predicted, and 3 structures are available. Although they catalyze the same chemical reaction, sequence similarity is low. To identify conserved regions, all EHs were aligned. Phylogenetic analysis identified 12 homologous families, which were grouped into 2 major superfamilies: the microsomal EH superfamily, which includes the homologous families of Mammalian, Insect, Fungal, and Bacterial EHs, and the cytosolic EH superfamily, which includes Mammalian, Plant, and Bacterial EHs. Bacterial EHs show a high sequence diversity. Based on structure comparison of three known structures from Agrobacterium radiobacter AD1 (cytosolic EH), Aspergillus niger (microsomal EH), Mus musculus (cytosolic EH), and multisequence alignment and phylogenetic analysis of 95 EHs, the modular architecture of this enzyme family was analyzed. Although core and cap domain are highly conserved, the structural differences between the EHs are restricted to only two loops: the NC-loop connecting the core and the cap and the cap-loop, which is inserted into the cap domain. EHs were assigned to either of three clusters based on loop length. By using this classification, core and cap region of all EHs, NC-loops and cap-loops of 78% and 89% of all EHs, respectively, could be modeled. Representative models are available from the Lipase Engineering Database, http://www.led.uni-stuttgart.de. (C) 2004Wiley-Liss, Inc.