title: Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.
abstract: The crystal structure of the human cyclinA-cyclin-dependent kinase2 (CDK2)-ATP complex has been determined at 2.3 A resolution. CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
authors.affiliation: Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Jeffrey
authors.forename: A A
authors.initials: AA
authors.lastname: Russo
authors.forename: K
authors.initials: K
authors.lastname: Polyak
authors.forename: E
authors.initials: E
authors.lastname: Gibbs
authors.forename: J
authors.initials: J
authors.lastname: Hurwitz
authors.forename: J
authors.initials: J
authors.lastname: Massagué
authors.forename: N P
authors.initials: NP
authors.lastname: Pavletich
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D001665:Binding Sites; D042846:CDC2-CDC28 Kinases; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000737:chemistry* / Q000378:metabolism; D016213:Cyclins / Q000737:chemistry* / Q000378:metabolism; D004789:Enzyme Activation; D004926:Escherichia coli; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D013912:Threonine / Q000737:chemistry
chemical_list: D016213:Cyclins; D011994:Recombinant Proteins; D013912:Threonine; D000255:Adenosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases