Stereoselective product inhibition of glutathione S-transferase

Isozymes 3-3 and 4-4 of rat liver glutathione S-transferase are stereoselectively inhibited by the diastereomers of 9,10-dihydro-9-glutathionyl-10-hydroxyphenanthrene, 1. The conformation of the biphenyl moiety is the same in the enzyme -1 complex as in aqueous solution with the glutathionyl and hydroxy groups in the axial positions. Isozyme 4-4 is also inhibited by the four diastereomers of 1,2-diphenyl-1-(S-glutathionyl)-2-hydroxyethane. The stereoselectivity of inhibition is modest in all cases and is manifest in both the type of inhibition as well as the magnitude of Ki.