Widersten M, Björnestedt R, Mannervik B
Department of Biochemistry, Uppsala University, Sweden.
Biochemistry. 1994 Oct 4;33(39):11717-23. doi: 10.1021/bi00205a007.
Glutathione transferases (GSTs) catalyze the nucleophilic attack of the thiolate of glutathione on a variety of noxious, often hydrophobic, electrophiles. The interactions responsible for the binding of glutathione have been deduced in great detail from the 3-dimensional structures that have been solved for three different GSTs, each a member of a distinct structural class. However, the interactions of the electrophilic substrates with these enzymes are still largely unexplored. The contribution of the active-site Met208 to aromatic and benzylic chloride substitution reactions catalyzed by human class Alpha GST A1-1 has been evaluated by comparison of wild-type enzyme with variants mutated in position 208. The results show that the amino acid residue at position 208 primarily affects the aromatic substitution reaction, tested with 1-chloro-2,4-dinitrobenzene as substrate, possibly by interacting with the delocalized negative charge of the substituted ring structure in the transition state.
谷胱甘肽转移酶（GSTs）催化谷胱甘肽硫醇盐对多种有毒的、通常为疏水性的亲电试剂进行亲核攻击。从已解析出三维结构的三种不同GSTs（每种都属于一个独特的结构类别）中，已经详细推导了负责谷胱甘肽结合的相互作用。然而，亲电底物与这些酶的相互作用在很大程度上仍未得到探索。通过将野生型酶与208位发生突变的变体进行比较，评估了活性位点的Met208对人α类GST A1-1催化的芳香族和苄基氯取代反应的贡献。结果表明，208位的氨基酸残基主要影响以1-氯-2,4-二硝基苯为底物测试的芳香族取代反应，可能是通过与过渡态中取代环结构的离域负电荷相互作用来实现的。
