The transfers of acyl, phosphoryl and sulfuryl groups are essential chemical processes in all biological systems. Phosphoryl transfer reactions constitute essential regulatory functions in the cell. Sulfate ester chemistry is critical in detoxification as well as in many regulatory pathways. Acyl transfer chemistry constitutes the key reaction in the building and in the decomposition of proteins. The goals of this project are to gain insight into the fundamental chemical and enzymatic mechanisms by which these reactions occur, and into the means by which enzymes catalyze these reactions. Some of our specific goals are: To determine the effects of solvation/desolvation on the kinetics and thermodynamics of phosphoryl and sulfuryl transfer reactions. To ascertain to what degree medium effects mimic the transfer of enzymatic phosphate and sulfate ester substrates from solution to active site, and to what degree such effects contribute to enzymatic catalysis. To determine whether """"""""substrate-assisted"""""""" catalysis occurs in enzyme-catalyzed phosphoryl or sulfuryl transfer reactions. To study the enzymatic mechanism of metallophosphatases, and determine the role of the binuclear metal center. We will determine if the binuclear metal center changes the mechanism of phosphoryl transfer, or if the reaction resembles that catalyzed by other phosphatases that do not utilize metal ions for catalysis. To characterize the mechanisms of sulfuryl transfer reactions, particularly of alkyl sulfate esters. We will determine the mechanism of enzymatic sulfuryl transfer by aryl sulfatase and by estrogen sulfotransferase. Continue our study of enzymatic acyl transfer reactions with more specific substrates. We will continue our study of how the mechanisms and transition states for enzymatic acyl transfer compare with those of uncatalyzed reactions.
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