Heterodimers of glutathione S-transferase can form between isoenzyme classes pi and mu.

Glutathione S-transferases constitute a family of enzymes that detoxify xenobiotics by conjugating glutathione with a range of electrophilic substrates. The cytosolic glutathione S-transferase dimeric isoenzymes are currently divided into at least eight classes on the basis of their physical and chemical properties. Previously, heterodimers have only been detected within a given class of isoenzymes; however, here we describe for the first time the generation of a heterodimer between a pi class and mu class glutathione S-transferase. The heterodimer forms under mild conditions (dialysis against phosphate buffer, pH 6.5) and is best detected when one of the isoenzyme subunits is in excess. The activity of the pi-mu heterodimer toward several substrates indicates that interaction between these two dissimilar subunits influences the catalytic activity of this dimer. The production of this new heterodimer provides a new approach in glutathione S-transferase research to study the influence of one subunit on the catalytic activity of its partner subunit and to identify those amino acid residues which contribute to subunit interactions. (c)2001 Elsevier Science.