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Design of fast enzymes by optimizing interaction potential in active site.

ABSTRACT: The diffusional encounter between substrate and enzyme, and hence catalytic efficiency, can be enhanced by mutating charged residues on the surface of the enzyme. In this paper we present a simple method for screening such mutations. This is based on our earlier result that electrostatic enhancement of the enzyme-substrate binding rate constant can be accounted for just by the interaction potential within the active site. Assuming that catalytic and structural integrity is maintained, the catalytic efficiency can be optimized by surface charge mutations which lead to stronger interaction potential within the active site. Application of the screening method on superoxide dismutase shows that only charge mutations close to the active site will have practical effect on the catalytic efficiency. This rationalizes a large number of findings obtained in previous simulation and experimental studies.

SUBMITTER: Zhou HX

PROVIDER: S-EPMC24950 | biostudies-literature | 1997 Nov

REPOSITORIES: biostudies-literature

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Design of fast enzymes by optimizing interaction potential in active site.

Zhou H X HX Wong K Y KY Vijayakumar M M

Proceedings of the National Academy of Sciences of the United States of America 19971101 23

The diffusional encounter between substrate and enzyme, and hence catalytic efficiency, can be enhanced by mutating charged residues on the surface of the enzyme. In this paper we present a simple method for screening such mutations. This is based on our earlier result that electrostatic enhancement of the enzyme-substrate binding rate constant can be accounted for just by the interaction potential within the active site. Assuming that catalytic and structural integrity is maintained, the cataly ...[more]

PMID: 9356456

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