Electrostatic recognition between superoxide and copper, zinc superoxide dismutase

Elizabeth D. Getzoff, John A. Tainer, Paul K. Weiner, Peter A. Kollman, Jane S. Richardson, David C. Richardson

Research output: Contribution to journalArticlepeer-review

476 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)287-290
Number of pages4
JournalNature
Volume306
Issue number5940
DOIs
StatePublished - 1983
Externally publishedYes

ASJC Scopus subject areas

  • General

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