Structural basis of cyclin-dependent kinase activation by phosphorylation (original) (raw)

Nature Structural Biology volume 3, pages 696–700 (1996)Cite this article

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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Authors and Affiliations

  1. Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, USA
    Alicia A. Russo, Philip D. Jeffrey & Nikola P. Pavletich

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  1. Alicia A. Russo
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  2. Philip D. Jeffrey
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  3. Nikola P. Pavletich
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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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