Molybdenum, an essential trace element, is the only metal in the second and third transition series that is essential for all forms of life. In humans, molybdoenzymes are involved in sulfite oxidation (sulfite oxidase) and purine metabolism (xanthine oxidase). Fatal simultaneous deficiencies in the activities of both of these enzymes due to an inborn deficiency of a common 'molybdenum cofactor' (Moco) are now well documented in children. Exposure to excess molybdenum has been linked with gout, and molybdenum deficiency may aggravate sensitivity to sulfite. The overall goal of this research is to understand the structure, function, and reactivity of this physiologically vital pterin-containing molybdenum enzyme through studies of model compounds and the enzyme itself. Sulfite oxidase is of fundamental interest to bioinorganic, biochemical and biophysical chemists because it provides opportunities to investigate the structure of the molybdenum cofactor, oxygen atom transfer chemistry, and intramolecular electron transfer reactions within a single molecular system. The research proposed here addresses these fundamental issues through an integrated program of synthetic, structural, spectroscopic and reactivity studies of model compounds and of sulfite oxidase itself. Emphasis will be given to the synthesis and characterization of models for the molybdenum-iron interaction in sulfite oxidase; to the development of electron spin echo envelope modulation (ESEEM) spectroscopy as a probe of the molybdenum environment in model compounds and enzymes; to studying intramolecular electron transfer between the molybdenum and iron centers of sulfite oxidase; and to initiating the determination of the structure of sulfite oxidase by X-ray crystallography.
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