Environment Research Institute, Shandong University , Jinan 250100, P. R. China.
Environ Sci Technol. 2014 May 6;48(9):5008-16. doi: 10.1021/es405230j. Epub 2014 Apr 8.
A combined quantum mechanics/molecular mechanics (QM/MM) computation of the detoxifying mechanism of an epsilon class glutathione transferases (GSTs) toward organochlorine insecticide DDT, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane, has been carried out. The exponential average barrier of the proton transfer mechanism is 15.2 kcal/mol, which is 27.6 kcal/mol lower than that of the GS-DDT conjugant mechanism. It suggests that the detoxifying reaction proceeds via a proton transfer mechanism where GSH acts as a cofactor rather than a conjugate. The study reveals that the protein environment has a strong effect on the reaction barrier. The experimentally proposed residues Arg112, Glu116 and Phe120 were found to have a strong influence on the detoxifying reaction. The influence of residues Pro13, Cys15, His53, Ile55, Glu67, Ser68, Phe115, and Leu119 was detected as well. It is worth noticing that Ile55 facilitates the detoxifying reaction most. On the basis of the structure of DDT, structure 2, (BrC6H4)2CHCCl3, is the best candidate among all the tested structures in resisting the detoxification of enzyme agGSTe2.
采用量子力学/分子力学（QM/MM）方法对 epsilon 类谷胱甘肽转移酶（GSTs）对有机氯杀虫剂滴滴涕（1,1,1-三氯-2,2-双（对氯苯基）乙烷）的解毒机制进行了计算。质子转移机制的指数平均势垒为 15.2 kcal/mol，比 GS-DDT 缀合物机制低 27.6 kcal/mol。这表明解毒反应通过质子转移机制进行，其中 GSH 作为辅因子而不是缀合物。该研究表明，蛋白质环境对反应势垒有很强的影响。实验提出的残基 Arg112、Glu116 和 Phe120 被发现对解毒反应有很强的影响。还检测到残基 Pro13、Cys15、His53、Ile55、Glu67、Ser68、Phe115 和 Leu119 的影响。值得注意的是，Ile55 最有利于解毒反应。基于 DDT 的结构，结构 2，（BrC6H4）2CHCCl3，是所有测试结构中抵抗酶 agGSTe2 解毒的最佳候选物。
