title: An inhibitor's-eye view of the ATP-binding site of CDKs in different regulatory states.
abstract: We have used a chemically diverse panel of kinase inhibitors to assess the chemical similarity of the ATP-binding sites of cyclin-dependent kinase (CDK) subfamily members in a range of activation states. Using this approach, we find that different activation states of a particular CDK may differ from each other as much as different CDKs in the same activation state. We also find that inhibitors discriminate more effectively among CDK family members in their monomeric state than in their cyclin-bound state, providing direct evidence for the belief that selective binding to inactive kinase states might be more readily achieved than selective binding to active states.
authors.affiliation: Laboratory of Molecular Biophysics, Department of Biochemistry, Oxford University , South Parks Road, Oxford OX1 3QU, United Kingdom.
authors.forename: Aude
authors.initials: A
authors.lastname: Echalier
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Hole
authors.forename: Graziano
authors.initials: G
authors.lastname: Lolli
authors.forename: Jane A
authors.initials: JA
authors.lastname: Endicott
authors.forename: Martin E M
authors.initials: ME
authors.lastname: Noble
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: D004791:Enzyme Inhibitors; D000255:Adenosine Triphosphate; D018844:Cyclin-Dependent Kinases