Structural basis of cyclin-dependent kinase activation by phosphorylation - PubMed (original) (raw)
Structural basis of cyclin-dependent kinase activation by phosphorylation
A A Russo et al. Nat Struct Biol. 1996 Aug.
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-ATP gamma S complex has been determined at 2.6 A 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 A, 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.
Similar articles
- Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.
Jeffrey PD, Russo AA, Polyak K, Gibbs E, Hurwitz J, Massagué J, Pavletich NP. Jeffrey PD, et al. Nature. 1995 Jul 27;376(6538):313-20. doi: 10.1038/376313a0. Nature. 1995. PMID: 7630397 - Effects of phosphorylation of threonine 160 on cyclin-dependent kinase 2 structure and activity.
Brown NR, Noble ME, Lawrie AM, Morris MC, Tunnah P, Divita G, Johnson LN, Endicott JA. Brown NR, et al. J Biol Chem. 1999 Mar 26;274(13):8746-56. doi: 10.1074/jbc.274.13.8746. J Biol Chem. 1999. PMID: 10085115 - Crystal structure of a viral cyclin, a positive regulator of cyclin-dependent kinase 6.
Schulze-Gahmen U, Jung JU, Kim SH. Schulze-Gahmen U, et al. Structure. 1999 Mar 15;7(3):245-54. doi: 10.1016/s0969-2126(99)80035-5. Structure. 1999. PMID: 10368294 - Structuring cell-cycle biology.
Levine K, Cross FR. Levine K, et al. Structure. 1995 Nov 15;3(11):1131-4. doi: 10.1016/s0969-2126(01)00248-9. Structure. 1995. PMID: 8591023 Review. - [The characterization of human cdc2 kinase and CDK2].
Yasuda H, Kamijo M, Ohba Y. Yasuda H, et al. Yakugaku Zasshi. 1993 Dec;113(12):829-46. doi: 10.1248/yakushi1947.113.12_829. Yakugaku Zasshi. 1993. PMID: 8301538 Review. Japanese.
Cited by
- Phosphatase PPM1A negatively regulates P-TEFb function in resting CD4(+) T cells and inhibits HIV-1 gene expression.
Budhiraja S, Ramakrishnan R, Rice AP. Budhiraja S, et al. Retrovirology. 2012 Jun 22;9:52. doi: 10.1186/1742-4690-9-52. Retrovirology. 2012. PMID: 22727189 Free PMC article. - Phosphorylation of CDK9 at Ser175 enhances HIV transcription and is a marker of activated P-TEFb in CD4(+) T lymphocytes.
Mbonye UR, Gokulrangan G, Datt M, Dobrowolski C, Cooper M, Chance MR, Karn J. Mbonye UR, et al. PLoS Pathog. 2013;9(5):e1003338. doi: 10.1371/journal.ppat.1003338. Epub 2013 May 2. PLoS Pathog. 2013. PMID: 23658523 Free PMC article. Clinical Trial. - Unveiling the noncanonical activation mechanism of CDKs: insights from recent structural studies.
Li T, Tang HC, Tsai KL. Li T, et al. Front Mol Biosci. 2023 Nov 9;10:1290631. doi: 10.3389/fmolb.2023.1290631. eCollection 2023. Front Mol Biosci. 2023. PMID: 38028546 Free PMC article. Review. - Structure of TFIIK for phosphorylation of CTD of RNA polymerase II.
van Eeuwen T, Li T, Kim HJ, Gorbea Colón JJ, Parker MI, Dunbrack RL, Garcia BA, Tsai KL, Murakami K. van Eeuwen T, et al. Sci Adv. 2021 Apr 7;7(15):eabd4420. doi: 10.1126/sciadv.abd4420. Print 2021 Apr. Sci Adv. 2021. PMID: 33827808 Free PMC article. - Identifying allosteric fluctuation transitions between different protein conformational states as applied to Cyclin Dependent Kinase 2.
Gu J, Bourne PE. Gu J, et al. BMC Bioinformatics. 2007 Feb 7;8:45. doi: 10.1186/1471-2105-8-45. BMC Bioinformatics. 2007. PMID: 17286863 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources
Molecular Biology Databases