Lewis David F V, Lake Brian G, Bird Michael G
School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK.
Toxicol In Vitro. 2005 Jun;19(4):517-22. doi: 10.1016/j.tiv.2004.07.001.
Homology modelling of the human microsomal epoxide hydrolase (EH) enzyme based on the fungal (Aspergillus niger) EH crystallographic template is reported. The active site lies in a well-defined, essentially hydrophobic, pocket within the overall enzyme structure. Two tyrosine residues, that are conserved in all known mammalian EH sequences, are able to form hydrogen bonds (one per tyrosine residue) with the epoxide oxygen atom on the known EH substrate, styrene oxide. There is also a small hydrophobic cleft, within the active site region, where the phenyl group of styrene oxide can bind, but this appears to be restricted such that the presence of bulky side-chains will render poor substrate status to the incoming epoxide molecule. Quantitative structure-activity relationship (QSAR) studies on a series of low molecular weight epoxides provide useful results which appear to be generally consistent with the human microsomal EH model, and thus may be used predictively for assessing the EH substrate and/or inhibitor status of untested compounds.
报道了基于真菌（黑曲霉）环氧水解酶（EH）晶体学模板对人微粒体环氧水解酶（EH）进行的同源建模。活性位点位于整个酶结构内一个定义明确、基本疏水的口袋中。在所有已知哺乳动物EH序列中保守的两个酪氨酸残基，能够与已知EH底物氧化苯乙烯上的环氧氧原子形成氢键（每个酪氨酸残基形成一个氢键）。在活性位点区域内还有一个小的疏水裂缝，氧化苯乙烯的苯基可以结合在那里，但这似乎受到限制，以至于庞大侧链的存在会使进入的环氧化物分子的底物状态变差。对一系列低分子量环氧化物的定量构效关系（QSAR）研究提供了有用的结果，这些结果似乎与人类微粒体EH模型总体上一致，因此可用于预测评估未测试化合物的EH底物和/或抑制剂状态。
