Structure and function of residue 104 and water molecules in the xenobiotic substrate-binding site in human glutathione S-transferase P1-1

Two variants of human class pi glutathione (GSH) S-transferase 1-1 with either isoleucine or valine in position 104 (hGSTP1-1(I104) and hGSTP1-1(V104)) have distinct activity toward (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene ((+)-anti-BPDE). The crystal structures of hGSTP1-1(I104)*GSBpd and hGSTP1-1(V104)*GSBpd showed that the half-hydrophilic and half-hydrophobic nature of the H-site is responsible for the enantioselectivity of hGSTP1-1 for (+)-anti-BPDE over (-)-anti-BPDE.