Abstract
Electrostatic forces have been implicated in a variety of biologically important molecular interactions including drug orientation by DNA1, protein folding2–3 and assembly4, substrate binding and catalysis5–7 and macromolecular complementarity with inhibitors, drugs and hormones8–11. 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 (O2−) 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 O2−, while Arg 141 has local orienting effects. The reported methods of analysis may have general application for the elucidation of inter-molecular recognition processes.
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Getzoff, E., Tainer, J., Weiner, P. et al. Electrostatic recognition between superoxide and copper, zinc superoxide dismutase. Nature 306, 287–290 (1983). https://doi.org/10.1038/306287a0
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DOI: https://doi.org/10.1038/306287a0
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