Structural basis of cyclin-dependent kinase activation by phosphorylation Journal Article
| Authors: | Russo, A. A.; Jeffrey, P. D.; Pavletich, N. P. |
| Article Title: | Structural basis of cyclin-dependent kinase activation by phosphorylation |
| 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. |
| Keywords: | nonhuman; protein conformation; animal cell; enzyme activation; enzyme activity; phosphorylation; enzyme phosphorylation; conserved sequence; protein-serine-threonine kinases; phosphoproteins; binding site; crystal structure; hydrogen bond; models, molecular; conformational transition; adenosine triphosphate; cyclin-dependent kinases; cyclins; cyclin a; cyclin dependent kinase; enzyme structure; enzyme substrate complex; enzyme subunit; crystallography; insect; cyclin-dependent kinase 2; cdc2-cdc28 kinases; priority journal; article |
| Journal Title: | Nature Structural Biology |
| Volume: | 3 |
| Issue: | 8 |
| ISSN: | 1072-8368 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1996-08-01 |
| Start Page: | 696 |
| End Page: | 700 |
| Language: | English |
| DOI: | 10.1038/nsb0896-696 |
| PUBMED: | 8756328 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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