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 language | English (US) |
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Pages (from-to) | 287-290 |
Number of pages | 4 |
Journal | Nature |
Volume | 306 |
Issue number | 5940 |
DOIs | |
State | Published - 1983 |
Externally published | Yes |
ASJC Scopus subject areas
- General