1h27: Difference between revisions
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'''CDK2/CYCLIN A IN COMPLEX WITH AN 11-RESIDUE RECRUITMENT PEPTIDE FROM P27''' | {{Structure | ||
|PDB= 1h27 |SIZE=350|CAPTION= <scene name='initialview01'>1h27</scene>, resolution 2.2Å | |||
|SITE= <scene name='pdbsite=AC1:Tpo+Binding+Site+For+Chain+C'>AC1</scene> | |||
|LIGAND= | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''CDK2/CYCLIN A IN COMPLEX WITH AN 11-RESIDUE RECRUITMENT PEPTIDE FROM P27''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1H27 is a [ | 1H27 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H27 OCA]. | ||
==Reference== | ==Reference== | ||
Specificity determinants of recruitment peptides bound to phospho-CDK2/cyclin A., Lowe ED, Tews I, Cheng KY, Brown NR, Gul S, Noble ME, Gamblin SJ, Johnson LN, Biochemistry. 2002 Dec 31;41(52):15625-34. PMID:[http:// | Specificity determinants of recruitment peptides bound to phospho-CDK2/cyclin A., Lowe ED, Tews I, Cheng KY, Brown NR, Gul S, Noble ME, Gamblin SJ, Johnson LN, Biochemistry. 2002 Dec 31;41(52):15625-34. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12501191 12501191] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: serine/threonine-protein kinase]] | [[Category: serine/threonine-protein kinase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:31:07 2008'' | ||
Revision as of 12:31, 20 March 2008
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CDK2/CYCLIN A IN COMPLEX WITH AN 11-RESIDUE RECRUITMENT PEPTIDE FROM P27
OverviewOverview
Progression through S phase of the eukaryotic cell cycle is regulated by the action of the cyclin dependent protein kinase 2 (CDK2) in association with cyclin A. CDK2/cyclin A phosphorylates numerous substrates. Substrate specificity often employs a dual recognition strategy in which the sequence flanking the phospho-acceptor site (Ser.Pro.X.Arg/Lys) is recognized by CDK2, while the cyclin A component of the complex contains a hydrophobic site that binds Arg/Lys.X.Leu ("RXL" or "KXL") substrate recruitment motifs. To determine additional sequence specificity motifs around the RXL sequence, we have performed X-ray crystallographic studies at 2.3 A resolution and isothermal calorimetry measurements on complexes of phospho-CDK2/cyclin A with a recruitment peptide derived from E2F1 and with shorter 11-mer peptides from p53, pRb, p27, E2F1, and p107. The results show that the cyclin recruitment site accommodates a second hydrophobic residue either immediately C-terminal or next adjacent to the leucine of the "RXL" motif and that this site makes important contributions to the recruitment peptide recognition. The arginine of the RXL motif contacts a glutamate, Glu220, on the cyclin. In those substrates that contain a KXL motif, no ionic interactions are observed with the lysine. The sequences N-terminal to the "RXL" motif of the individual peptides show no conservation, but nevertheless make common contacts to the cyclin through main chain interactions. Thus, the recruitment site is able to recognize diverse but conformationally constrained target sequences. The observations have implications for the further identification of physiological substrates of CDK2/cyclin A and the design of specific inhibitors.
DiseaseDisease
Known diseases associated with this structure: Multiple endocrine neoplasia, type IV OMIM:[600778]
About this StructureAbout this Structure
1H27 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Specificity determinants of recruitment peptides bound to phospho-CDK2/cyclin A., Lowe ED, Tews I, Cheng KY, Brown NR, Gul S, Noble ME, Gamblin SJ, Johnson LN, Biochemistry. 2002 Dec 31;41(52):15625-34. PMID:12501191
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