The ligandin (non-substrate) binding site of human Pi class glutathione transferase is located in the electrophile binding site (H-site)

Citation
Aj. Oakley et al., The ligandin (non-substrate) binding site of human Pi class glutathione transferase is located in the electrophile binding site (H-site), J MOL BIOL, 291(4), 1999, pp. 913-926
Citations number
61
Categorie Soggetti
Molecular Biology & Genetics
Journal title
JOURNAL OF MOLECULAR BIOLOGY
ISSN journal
00222836 → ACNP
Volume
291
Issue
4
Year of publication
1999
Pages
913 - 926
Database
ISI
SICI code
0022-2836(19990827)291:4<913:TL(BSO>2.0.ZU;2-3
Abstract
Glutathione S-transferases (GSTs) play a pivotal role in the detoxification of foreign chemicals and toxic metabolites. They were originally termed li gandins because of their ability to bind large molecules (molecular masses >400 Da), possibly for storage and transport roles. The location of the lig andin site in mammalian GSTs is still uncertain despite numerous studies in recent years. Here we show by X-ray crystallography that the ligandin bind ing site in human pi class GST P1-1 occupies part of one of the substrate b inding sites. This work has been extended to the determination of a number of enzyme complex crystal structures which show that very large ligands are readily accommodated into this substrate binding site and in all, but one case, causes no significant movement of protein side-chains. Some of these molecules make use of a hitherto undescribed binding site located in a surf ace pocket of the enzyme. This site is conserved in most, but not all, clas ses of GSTs suggesting it may play an important functional role. (C) 1999 A cademic Press.