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
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.