Structural basis for chemical inhibition of CDK2.
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 inhibitors. In this article five structures of human CDK2 are summarised: apoprotein, ATP complex, olomoucine complex, isopentenyladenine complex, and des-chloro-flavopiridol complex.
Kim
S H
SH
Department of Chemistry, Lawrence Berkeley National Laboratory, University of California 94720, USA.
Schulze-Gahmen
U
U
Brandsen
J
J
de Azevedo Júnior
W F
WF
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle; D018360:Crystallography, X-Ray; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007541:Isopentenyladenosine; D007701:Kinetin; D008024:Ligands; D046911:Macromolecular Substances; D008958:Models, Molecular; D010880:Piperidines / Q000494:pharmacology; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011687:Purines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry
D004791:Enzyme Inhibitors; D005419:Flavonoids; D008024:Ligands; D046911:Macromolecular Substances; D010880:Piperidines; D011687:Purines; D011994:Recombinant Proteins; C001478:N(6)-(delta(2)-isopentenyl)adenine; C077990:alvocidib; C090046:olomoucine; D007541:Isopentenyladenosine; D000255:Adenosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D000225:Adenine; D007701:Kinetin