Abstract
Cyclin-dependent kinase (CDK)–cyclin complexes require phosphorylation on the CDK subunit for full activation of their Ser/Thr protein kinase activity. The crystal structure of the phosphorylated CDK2–CyclinA–ATPγS complex has been determined at 2.6 Å resolution. The phosphate group, which is on the regulatory T-loop of CDK2, is mostly buried, its charge being neutralized by three Arg side chains. The arginines help extend the influence of the phosphate group through a network of hydrogen bonds to both CDK2 and cyclinA. Comparison with the unphosphorylated CDK2–CyclinA complex shows that the T-loop moves by as much as 7 Å, and this affects the putative substrate binding site as well as resulting in additional CDK2–CyclinA contacts. The phosphate group thus acts as a major organizing centre in the CDK2–CyclinA complex.
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Russo, A., Jeffrey, P. & Pavletich, N. Structural basis of cyclin-dependent kinase activation by phosphorylation. Nat Struct Mol Biol 3, 696–700 (1996). https://doi.org/10.1038/nsb0896-696
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DOI: https://doi.org/10.1038/nsb0896-696
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