Theoretical study of the full reaction mechanism of human soluble epoxide hydrolase
Theoretical study of the full reaction mechanism of human soluble epoxide hydrolase
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DOI：
10.1002/chem.200501519
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发表时间：
2006-09-06
影响因子：
4.3
通讯作者：
Himo, Fahmi
中科院分区：
文献类型：
--
作者：
Hopmann, Kathrin H.;Himo, Fahmi
利用B3LYP密度泛函理论方法研究了可溶性环氧化物水解酶(sEH)的完整反应机理。环氧化物水解酶催化环氧化物转化为其相应的邻位二醇。在我们的理论研究中，sEH 活性位点由基于人类可溶性环氧化物水解酶的 X 射线晶体结构的量子化学模型表示。反式取代的环氧化物(1S,2S)-β-甲基氧化苯乙烯已被用作sEH反应机理的理论研究的底物。烷基化和水解半反应都得到了详细研究。我们介绍了反应机理的能量学以及优化的中间体和过渡态结构。已经计算了涉及 (1S,2S)-β-甲基苯乙烯氧化物的苯甲基或均苯甲基碳原子的亲核攻击反应的完整势能曲线。已经解决了两种底物 (1S,2S)-β-甲基氧化苯乙烯和 (S)-氧化苯乙烯的环氧化物开环的区域选择性问题。
The complete reaction mechanism of soluble epoxide hydrolase (sEH) has been investigated by using the B3LYP density functional theory method. Epoxide hydrolases catalyze the conversion of epoxides to their corresponding vicinal diols. In our theoretical study, the sEH active site is represented by quantum-chemical models that are based on the X-ray crystal structure of human soluble epoxide hydrolase. The trans-substituted epoxide (1S,2S)-beta-methyl styrene oxide has been used as a substrate in the theoretical investigation of the sEH reaction mechanism. Both the alkylation and the hydrolytic half-reactions have been studied in detail. We present the energetics of the reaction mechanism as well as the optimized intermediates and transition-state structures. Full potential energy curves for the reactions involving nucleophilic attack at either the benzylic or the homo-benzylic carbon atom of (1S,2S)-beta-methylstyrene oxide have been computed. The regioselectivity of epoxide opening has been addressed for the two substrates (1S,2S)-beta-methylstyrene oxide and (S)-styrene oxide.