Structural bioinformatics study of cyclin-dependent kinases complexed with inhibitors

Structural Bioinformatics Study of Cyclin-dependent Kinases Complexed with Inhibitors

Cell cycle progression is tightly controlled by the activity of cyclin-dependent kinases (CDKs) [31]. CDKs are inactive as monomers, and activation requires binding to cyclins, a diverse family of proteins whose levels oscillate during the cell cycle, and phosphorylation by CDK-activating kinase (CAK) on a specific threonine residue [19]. In addition to the positive regulatory role of cyclins a...

Pharmacological inhibitors of cyclin-dependent kinases.

Cyclin-dependent kinases (CDKs) regulate the cell division cycle, apoptosis, transcription and differentiation in addition to functions in the nervous system. Deregulation of CDKs in various diseases has stimulated an intensive search for selective pharmacological inhibitors of these kinases. More than 50 inhibitors have been identified, among which >20 have been co-crystallized with CDK2. Thes...

Inhibitors of mammalian G1 cyclin-dependent kinases.

Inhibition of cyclin-dependent kinases by purine analogues: crystal structure of human cdk2 complexed with roscovitine.

Cyclin-dependent kinases (cdk) control the cell division cycle (cdc). These kinases and their regulators are frequently deregulated in human tumours. A potent inhibitor of cdks, roscovitine [2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurin e], was identified by screening a series of C2,N6,N9-substituted adenines on purified cdc2/cyclin B. Roscovitine displays high efficiency and h...

Mammalian cyclin-dependent kinases.

Cyclin-dependent kinases (Cdks) are the catalytic subunits of a family of mammalian heterodimeric serine/threonine kinases that have been implicated in the control of cell-cycle progression, transcription and neuronal function. Recent genetic evidence obtained with gene-targeted mice has shown that Cdk4 and Cdk6 are not needed for entry into the cell cycle after mitogenic stimuli and organogene...