Evidence for the involvement of histidine at the active site of glutathione S-transferase psi from human liver.

The inhibition of catalytic activity of glutathione S-transferase psi (pI 5.5) of human liver by diethylpyrocarbonate (DEPC) has been studied. It is demonstrated that DEPC causes a concentration dependent inactivation of GST psi with a concomitant modification of 1-1.3 histidyl residues/subunit of the enzyme. This inactivation of GST psi could be reversed by treatment with hydroxylamine. Glutathione afforded complete protection to the enzyme from inactivation by DEPC. It is suggested that a functional histidyl residue is essential for the catalytic activity of the enzyme and that this residue is most likely to be present at or near the glutathione binding site (G-site).