Thirty Years of Structural Studies on Cyclin-Dependent Kinases: Implications for Drug Discovery

Abstract

Cyclin-dependent Kinases (CDKs) (EC 2.7.11.22) comprise a group of Serine/Threonine kinases [1, 2] involved in several cellular processes ranging from cell cycle progression to differentiation of nerve cells. CDKs also have roles in regulating transcription and senescence. In the human genome, 20 CDKs have been identified [3]. Due to its pivotal function in controlling the cell cycle progression in eukaryotes, CDK2 has been the subject of functional and structural studies in the last decades [4]. The critical role of CDK2 in cancer motivated extensive crystallographic analyses to support Structure-Based Drug Design (SBDD). In 1993, the high-resolution crystal structures of CDK2, both in its apo form and in complex with ATP, provided the first detailed view of this important therapeutic target.