Design of fast enzymes by optimizing interaction potential in active site

AUTOR(ES)

Zhou, Huan-Xiang

FONTE

The National Academy of Sciences of the USA

RESUMO

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.

Documentos Relacionados

• A method for optimizing potential-energy functions by a hierarchical design of the potential-energy landscape: Application to the UNRES force field
• Shared active sites in oligomeric enzymes: model studies with defective mutants of aspartate transcarbamoylase produced by site-directed mutagenesis.
• Demonstration of the in vivo interaction of key cell death regulators by structure-based design of second-site suppressors
• Active-site zinc ligands and activated H2O of zinc enzymes.
• Optimizing dissolved air flotation design system