The importance of adenylate cyclase in the regulation and mediation of a diverse array of biological and biochemical processes requires that the chemical mechanism of the reaction it catalyzes be understood. This information may allow the design and synthesis of novel suicide inhibors of the enzyme which can be used both in vitro and in vivo to better understand the mechanisms by which cyclic nucleotides exert their effects. In order to characterize the mechanism of adenylate cyclase, we are preparing ATP which is oxygen chiral at either the alpha- or beta-phosphorus atom; these materials will be useful in additional stereochemical studies of the reaction and in defining the role of metal ions in catalysis. We also plan to determine whether adenylate cyclase contains tightly bound metal ions which are required for activity, since our preliminary experiments and data available for enzymes which catalyze similar reactions indicate that such metal ions may be absolutely required for catalytic activity.

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National Institute of General Medical Sciences (NIGMS)
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University of Maryland College Park
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