Structure-based inhibitor design for CDK2, a cell cycle controlling protein kinase

Abstract

The central role of cyclin-dependent kinases (CDKs) in cell cycle regulation makes them a promising target for discovering small inhibitory molecules that can modify the degree of cell proliferation. The three-dimensional structure of CDK2 provides a structural foundation for understanding the mechanisms of activation and inhibition of CDK2 and for the discovery of the inhibitors. In this presentation five structures of human CDK2 are summarized: apo protein, ATP complex, olomoucine complex, isopentenyladenine complex, and flavopiridol complex. This structural information is used for the design of a small, directed combinatorial library.