David N. Silverman, Ph.D.
Distinguished Professor
Pharmacology
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David N. Silverman, Ph.D. |
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Structure and kinetics of rapid enzymes: carbonic anhydrase and superoxide dismutase Dr. Silverman's lab studies the catalytic mechanism of two very fast enzymes, carbonic anhydrase and superoxide dismutase. We ask what accounts for the extraordinary efficiency of these enzymes, which are able to convert the substrates carbon dioxide and superoxide to products with catalytic turnovers as great as one million per second. Both enzymes are involved in critical physiological processes. The carbonic anhydrases comprise many isoforms in humans that convert carbon dioxide into bicarbonate to form secretory fluids, and in the red cells function during respiration. The superoxide dismutases convert superoxide, a toxic by-product of many enzymatic reactions, into hydrogen peroxide and oxygen. With carbonic anhydrase our work focuses mainly on the mechanism of proton transfer in the active site. In the pathway, protons must be transferred from the zinc-bound water to solution at a rate at least as fast as a million per second. We have measured the rates of intramolecular proton transfer in many isozymes and site-specific mutants of carbonic anhydrase to understand what processes determine the activation barrier for this proton transfer rate. This is a very good system for studying such proton transfers, and the properties of intramolecular proton transfer that we discover should be applicable to more complex systems such as bacteriorhodopsin, cytochrome c oxidase, and F0F1 ATPase, among others. Our work with manganese superoxide dismutase is to determine the pathway and rates of the proton transfers that form the product hydrogen peroxide. This enzyme has a network of hydrogen-bonded water and side chains that extend throughout the active site. Our work with site-specific mutants has determined that this network plays a critical role in these proton transfers. Under many conditions, manganese superoxide dismutase is limited in rate by a product inhibition. Using a variety of methods, we are measuring the rates of formation of the inhibited complex and identifying its structure.
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Status: Not Accepting New Students This Year Contact Information: office: R5-106 lab: R5-175 phone: 352-392 3556 email: silvrmn@ufl.edu Home Page Biography: David Silverman received a Ph.D. with Professor Benjamin P. Dailey at Columbia University and did postdoctoral work with Professor Harold A. Scheraga at Cornell University. Since 1971 he has worked at the University of Florida where he is now Distinguished Professor. His research interests include catalytic mechanisms of the rapid enzymes carbonic anhydrase and superoxide dismutase and the reactions of nitric oxide. |
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