RELATION OF STRUCTURE TO FUNCTION OF ENZYMES

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We propose to continue our studies on the structure and function of enzymes involved in the regulating of carbohydrate metabolism in relation to hormone action and muscle contraction. Specifically, we are interested in: 1) The architecture of phosphorylase phosphatase, an enzyme that might play a central role in the control of glycogen synthesis and breakdown and the possible involvement of insulin in its regulation. The enzyme exists in an inactive form and the various mechanisms by which it can be activated are being investigated. 2) Crystallizing the cAMP-dependent protein kinase catalytic subunit and determining the structure and function of phosphorylase kinase with particular emphasis on the characterization of its catalytic sites and the role of its other subunits. 3) The structure and physiological function of a heat-stable protein inhibitor of protein kinase that has been isolated from skeletal muscle. A new project concerned with microtubule cold-stability has been initiated. Attempts are being made to isolate and characterize a number of microtubule-associated proteins involved in this process and to determine how their activity might be modulated by phosphorylation-dephosphorylation reactions catalyzed by calmodulin-dependent and independent kinases.