SHIFTING SUBSTRATE-SPECIFICITY OF HUMAN GLUTATHIONE TRANSFERASE (FROMCLASS-PI TO CLASS-ALPHA) BY A SINGLE-POINT MUTATION

Substrate selectivity, among glutathione transferase (GST) isoenzymes, appears to be determined by a few residues. As part of study to deter mine which residues are class-specific determinants, Tyr 108 (an impor tant residue of the class Pi) has been changed to a valine, the struct ural equivalent of a class Alpha enzyme. Using a panel of selected sub strates, ''diagnostic'' for either class Pi or Alpha, it is shown here that this single mutation significantly alters the catalytic properti es of the class Pi enzyme and shifts the substrate specificity of the enzyme toward that of the class Alpha enzyme. (C) 1998 Academic Press.