Electrostatic recognition between superoxide and copper, zinc superoxide dismutase.
Electrostatic forces have been implicated in a variety of biologically important molecular interactions including drug orientation by DNA, protein folding and assembly, substrate binding and catalysis and macromolecular complementarity with inhibitors, drugs and hormones. To examine enzyme-substrate interactions in copper, zinc superoxide dismutase (SOD), we developed a method for the visualization and analysis of an enzyme's three-dimensional electrostatic vector field that allows the contributions of specific residues to be identified. We report here that the arrangement of electrostatic charges in SOD promotes productive enzyme-substrate interaction through substrate guidance and charge complementarity: sequence-conserved residues create an extensive electrostatic field that directs the negatively charged superoxide (O-2) substrate to the highly positive catalytic binding site at the bottom of the active-site channel. Dissection of the electrostatic potential gradient indicated the relative contributions of individual charged residues: Lys 134 and Glu 131 seem to have important roles in directing the long-range approach of O-2, while Arg 141 has local orienting effects. The reported methods of analysis may have general application for the elucidation of intermolecular recognition processes.
D001665:Binding Sites; D003300:Copper; D004560:Electricity; D006863:Hydrogen-Ion Concentration; D007477:Ions; D008958:Models, Molecular; D011487:Protein Conformation; D013482:Superoxide Dismutase; D015032:Zinc
D007477:Ions; D003300:Copper; D013482:Superoxide Dismutase; D015032:Zinc