9304940 Eisenstein The goal of this research is the elucidation of a molecular mechanism of control for the allosteric enzyme threonine deaminase from E. coli, with particular emphasis on the regulation of enzyme activity by the small heterotropic effectors isoleucine and valine. Our approach consists of characterizing the effects of regulatory ligands on both substrate binding and catalysis, and then combining the information with experimental measurements of heterotropic effector-promoted global, and local, conformational changes to ultimately provide a molecular explanation of control by feedback inhibition. %%% The activities of enzymes involved at junctures between metabolic pathways are often controlled by substrate and product concentrations as well as by products of other pathways. This proposal is significant in that it involves extensive work on the characteristic enzyme-associated mechanistic specificity of an allosterically controlled system, a pyridoxal phosphate-dependent enzyme, threonine deaminase. These studies involve sophisticated kinetic and structural studies which in their synthesis will yield a model relating enzyme structure and binding to alterations in kinetic behavior. This would be a great achievement. ***
