STRUCTURAL BASIS FOR FUNCTIONAL PROPERTIES OF PIN 1

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This research program is to address the structural basis for the function of Pin-1 through X-ray crystallographic studies combined with energetic measurements of substrate binding. These studies focus on understanding the chemical mechanism of peptidyl-prolyl isomerization, the basis for molecular specificity of this active site, and ultimately the detailed description of Pin-1-dependent regulation of cell cycle proteins. This work may result in the rational or combinatorial development of lipophilic small molecule inhibitors of Pin-1 that should be effective chemotherapeutic agents against neoplastic diseases resulting from unregulated cell growth.