This starter grant award to the University of Delaware supports the research of Professor Eugene G. Mueller. The research is an investigation of the mechanism and structure of the enzyme myo-inositol oxygenase, whose catalytic function arises from a non-heme iron in a protein environment. Techniques employed include nuclear magnetic resonance and Moessbauer spectroscopies; rapid freeze quench methods; site-directed mutagenesis; and steady-state and rapid kinetic studies including substrate analogs, inhibitors, and the determination of isotope effects. In addition to the novel chemistry to emerge from these studies, the enzyme myo-inositol oxygenase is of physiological interest. Diabetic animals show a marked decrease in its acitivity, and inhibition of the enzyme leads to rapid kidney failure. Inositol phosphates play a key role in cellular signaling, errors in which mediate oncogenesis. Thus, non-heme, iron-containing enzymes are vital in life-sustaining biological processes.
