Effect of local environment and protein on the mechanism of action of superoxide dismutase.

Quantum mechanical simulations of the mechanism of action of superoxide dismutase (SOD) indicate that the presence of Arg-141 in the active site of the enzyme is responsible for the formation of an intermediate complex between superoxide and the enzyme in which the copper is not reduced. The analysis of the local environmental effects of Arg-141 shows that this residue prevents the reduction of copper by forming a hydrogen bond to superoxide and by generating an electric field in the active site that opposes the transfer of an electron from superoxide to copper. The protein enhances the effect of the opposing field generated by Arg-141. Local changes in the environment of the copper ion, simulated by stretching the Cu-NE2 (His-61) bond also do not induce an electron transfer from superoxide to copper. The protein increases the energies required for this stretch through the electric field it generates near the active site. These results are further support for the new proposed mechanism of action of SOD which is based on the inability of superoxide to reduce the cupric ion in the enzyme.