Electrostatic recognition between superoxide and copper, zinc superoxide dismutase.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Getzoff, ED; Tainer, JA; Weiner, PK; Kollman, PA; Richardson, JS; Richardson, DC

Published Date

  • November 17, 1983

Published In

Volume / Issue

  • 306 / 5940

Start / End Page

  • 287 - 290

PubMed ID

  • 6646211

Pubmed Central ID

  • 6646211

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/306287a0

Language

  • eng

Conference Location

  • England