Chen Liqing, Hall Pamela R, Zhou Xiaoyin E, Ranson Hilary, Hemingway Janet, Meehan Edward J
Laboratory for Structural Biology, Department of Chemistry, Graduate Programs of Biotechnology, Chemistry and Materials Science, University of Alabama in Huntsville, Huntsville, AL 35899, USA.
Acta Crystallogr D Biol Crystallogr. 2003 Dec;59(Pt 12):2211-7. doi: 10.1107/s0907444903018493. Epub 2003 Nov 27.
Glutathione S-transferases (GSTs) are a major family of detoxification enzymes which possess a wide range of substrate specificities. Most organisms possess many GSTs belonging to multiple classes. Interest in GSTs in insects is focused on their role in insecticide resistance; many resistant insects have elevated levels of GST activity. In the malaria vector Anopheles gambiae, elevated GST levels are associated with resistance to the organochlorine insecticide DDT [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane]. This mosquito is the source of an insect GST, agGSTd1-6, which metabolizes DDT and is inhibited by a number of pyrethroid insecticides. The crystal structure of agGSTd1-6 in complex with its inhibitor S-hexyl glutathione has been determined and refined at 2.0 A resolution. The structure adopts a classical GST fold and is similar to those of other insect delta-class GSTs, implying a common conjugation mechanism. A structure-based model for the binding of DDT to agGSTd1-6 reveals two subpockets in the hydrophobic binding site (H-site), each accommodating one planar p-chlorophenyl ring.
谷胱甘肽S-转移酶（GSTs）是主要的解毒酶家族，具有广泛的底物特异性。大多数生物体拥有许多属于多个类别的GSTs。对昆虫GSTs的研究兴趣集中在它们在抗杀虫剂方面的作用；许多抗性昆虫的GST活性水平升高。在疟疾媒介冈比亚按蚊中，GST水平升高与对有机氯杀虫剂滴滴涕（1,1,1-三氯-2,2-双（对氯苯基）乙烷）的抗性有关。这种蚊子是昆虫GST——agGSTd1-6的来源，它能代谢滴滴涕并被多种拟除虫菊酯类杀虫剂抑制。已确定并以2.0埃分辨率精修了与抑制剂S-己基谷胱甘肽复合的agGSTd1-6的晶体结构。该结构采用经典的GST折叠，与其他昆虫δ-类GSTs的结构相似，这意味着存在共同的共轭机制。基于结构的滴滴涕与agGSTd1-6结合模型揭示了疏水结合位点（H位点）中的两个亚口袋，每个亚口袋容纳一个平面对氯苯基环。
