Structure and Function of Metal-Dependent Protein Phosphatases

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

Information on the conformation of the B-loop, critical for substrate recognition, would greatly aid development of specific inhibitors of Wip1 phosphatase activity. Additionally, high-resolution structural information for the Wip1 catalytic site would be useful for optimization of known inhibitors and to guide structure-activity investigations of inhibitors or activators identified in high-throughput studies. To that end, we have continued optimizing the expression of recombinant Wip1, identifying aggregation-prone residues, and screening for crystallization conditions in collaboration with Drs. Ettore Appella and Jay Kumar, Laboratory of Cell Biology, NCI. We anticipate that these systematic efforts will provide the first structure of Wip1 to help better understand the specificity and potential for inhibition.