DETERMINANTS OF CKS SUBSTRATE SPECIFICITY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Cyclin dependent kinases (Cdk) are critical regulators of the cell cycle and are upregulated in many cancers. Cks is a Cdk subunit that is known to bind phosphate. We are exploring Cks as a substrate targeting subunit that brings Cdk to substrates already primed by phosphorylation. The specific goal of these crystallographic studies is to solve the structure of Cks bound to phosphopeptides to understand the molecular basis for substrate specificity.