Computational Evidence for the Detoxifying Mechanism of Epsilon Class Glutathione Transferase Toward the Insecticide DDT

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• 作者：Yanwei Li ; Xiangli Shi ; Qingzhu Zhang ; Jingtian Hu ; Jianmin Chen ; Wenxing Wang
• 刊名：Environmental Science & Technology
• 出版年：2014
• 出版时间：May 6, 2014
• 年：2014
• 卷：48
• 期：9
• 页码：5008-5016
• 全文大小：553K
• 年卷期：v.48,no.9(May 6, 2014)
• ISSN：1520-5851

文摘

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.