An Inhibitor’s-Eye View of the ATP-Binding
Site of CDKs in Different Regulatory States
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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