Crystal structures and kinetic studies of human Kappa class glutathione transferase provide insights into the catalytic mechanism

	Crystal structures and kinetic studies of human Kappa class glutathione transferase provide insights into the catalytic mechanism
	Wang, B; Peng, YJ; Zhang, TL; Ding, JP
刊名	BIOCHEMICAL JOURNAL
	2011
卷号	439 期号:1 页码:215-225
关键词	catalytic mechanism conformational change crystal structure Kappa class glutathione transferase (GSTk) kinetic measurement substrate-binding pocket
通讯作者	Ding, JP (reprint author), Chinese Acad Sci, State Key Lab Mol Biol, Shanghai 200031, Peoples R China.,jpding@sibs.ac.cn
英文摘要	GSTs (glutathione transferases) are a family of enzymes that primarily catalyse nucleophilic addition of the thiol of GSH (reduced glutathione) to a variety of hydrophobic electrophiles in the cellular detoxification of cytotoxic and genotoxic compounds. GSTks (Kappa class GSTs) are a distinct class because of their unique cellular localization, function and structure. In the present paper we report the crystal structures of hGSTk (human GSTk) in apo-form and in complex with GTX (S-hexylglutathione) and steady-state kinetic studies, revealing insights into the catalytic mechanism of hGSTk and other GSTks. Substrate binding induces a conformational change of the active site from an 'open' conformation in the apo-form to a 'closed' conformation in the GTX-bound complex, facilitating formations of the G site (GSH-binding site) and the H site (hydrophobic substrate-binding site). The conserved Ser(16) at the G site functions as the catalytic residue in the deprotonation of the thiol group and the conserved Asp(69), Ser(200), Asp(201) and Arg(202) form a network of interactions with gamma-glutamyl carboxylate to stabilize the thiolate anion. The H site is a large hydrophobic pocket with conformational flexibility to allow the binding of different hydrophobic substrates. The kinetic mechanism of hGSTk conforms to a rapid equilibrium random sequential Bi Bi model.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	THIOREDOXIN-LIKE DOMAIN ; S-TRANSFERASE ; DISULFIDE-BOND ; ENZYME ; ALPHA ; EVOLUTION ; P1-1 ; SIMILARITY ; REVEALS ; RESIDUE
收录类别	SCI
语种	英语
WOS记录号	WOS:000296123800004
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/911]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Wang, B,Peng, YJ,Zhang, TL,et al. Crystal structures and kinetic studies of human Kappa class glutathione transferase provide insights into the catalytic mechanism[J]. BIOCHEMICAL JOURNAL,2011,439(1):215-225.
APA	Wang, B,Peng, YJ,Zhang, TL,&Ding, JP.(2011).Crystal structures and kinetic studies of human Kappa class glutathione transferase provide insights into the catalytic mechanism.BIOCHEMICAL JOURNAL,439(1),215-225.
MLA	Wang, B,et al."Crystal structures and kinetic studies of human Kappa class glutathione transferase provide insights into the catalytic mechanism".BIOCHEMICAL JOURNAL 439.1(2011):215-225.