9723372 Koshland This project is designed to change the specificity of an enzyme by substitution of amino acids at the active site or in other parts of the protein by site-directed mutation or by random mutation. The purpose is to create an enzyme that has the same catalytic power but a very different specificity from the original enzyme. The enzyme chosen for this study is isocitrate dehydrogenase, a key enzyme in the Krebs cycle and it is to be changed into an alkylmalate dehydrogenase, a change that alters the active site from a polar, negatively charged chain to a non-polar, hydrophobic side chain. To change the specificity of an enzyme is of great significance both for research and applied practical problems. To apply enzyme catalysis to practical problems such as cleanup of toxic wastes, it will be important to direct the catalytic power of an enzyme towards specific compounds such as man-made polutants that need removal. ***
