1w98
From Proteopedia
(New page: 200px<br /> <applet load="1w98" size="450" color="white" frame="true" align="right" spinBox="true" caption="1w98, resolution 2.15Å" /> '''THE STRUCTURAL BASI...) |
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| - | [[Image:1w98.gif|left|200px]]<br /> | + | [[Image:1w98.gif|left|200px]]<br /><applet load="1w98" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1w98" size=" | + | |
caption="1w98, resolution 2.15Å" /> | caption="1w98, resolution 2.15Å" /> | ||
'''THE STRUCTURAL BASIS OF CDK2 ACTIVATION BY CYCLIN E'''<br /> | '''THE STRUCTURAL BASIS OF CDK2 ACTIVATION BY CYCLIN E'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Cyclin E, an activator of phospho-CDK2 (pCDK2), is important for cell | + | Cyclin E, an activator of phospho-CDK2 (pCDK2), is important for cell cycle progression in metazoans and is frequently overexpressed in cancer cells. It is essential for entry to the cell cycle from G0 quiescent phase, for the assembly of prereplication complexes and for endoreduplication in megakaryotes and giant trophoblast cells. We report the crystal structure of pCDK2 in complex with a truncated cyclin E1 (residues 81-363) at 2.25 A resolution. The N-terminal cyclin box fold of cyclin E1 is similar to that of cyclin A and promotes identical changes in pCDK2 that lead to kinase activation. The C-terminal cyclin box fold shows significant differences from cyclin A. It makes additional interactions with pCDK2, especially in the region of the activation segment, and contributes to CDK2-independent binding sites of cyclin E. Kinetic analysis with model peptide substrates show a 1.6-fold increase in kcat for pCDK2/cyclin E1 (81-363) over kcat of pCDK2/cyclin E (full length) and pCDK2/cyclin A. The structural and kinetic results indicate no inherent substrate discrimination between pCDK2/cyclin E and pCDK2/cyclin A with model substrates. |
==About this Structure== | ==About this Structure== | ||
| - | 1W98 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http:// | + | 1W98 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W98 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Dubinina, E.]] | [[Category: Dubinina, E.]] | ||
[[Category: Honda, R.]] | [[Category: Honda, R.]] | ||
| - | [[Category: Johnson, L | + | [[Category: Johnson, L N.]] |
| - | [[Category: Lowe, E | + | [[Category: Lowe, E D.]] |
[[Category: Skamnaki, V.]] | [[Category: Skamnaki, V.]] | ||
[[Category: cell cycle]] | [[Category: cell cycle]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:41:47 2008'' |
Revision as of 13:41, 21 February 2008
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THE STRUCTURAL BASIS OF CDK2 ACTIVATION BY CYCLIN E
Overview
Cyclin E, an activator of phospho-CDK2 (pCDK2), is important for cell cycle progression in metazoans and is frequently overexpressed in cancer cells. It is essential for entry to the cell cycle from G0 quiescent phase, for the assembly of prereplication complexes and for endoreduplication in megakaryotes and giant trophoblast cells. We report the crystal structure of pCDK2 in complex with a truncated cyclin E1 (residues 81-363) at 2.25 A resolution. The N-terminal cyclin box fold of cyclin E1 is similar to that of cyclin A and promotes identical changes in pCDK2 that lead to kinase activation. The C-terminal cyclin box fold shows significant differences from cyclin A. It makes additional interactions with pCDK2, especially in the region of the activation segment, and contributes to CDK2-independent binding sites of cyclin E. Kinetic analysis with model peptide substrates show a 1.6-fold increase in kcat for pCDK2/cyclin E1 (81-363) over kcat of pCDK2/cyclin E (full length) and pCDK2/cyclin A. The structural and kinetic results indicate no inherent substrate discrimination between pCDK2/cyclin E and pCDK2/cyclin A with model substrates.
About this Structure
1W98 is a Protein complex structure of sequences from Homo sapiens. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
The structure of cyclin E1/CDK2: implications for CDK2 activation and CDK2-independent roles., Honda R, Lowe ED, Dubinina E, Skamnaki V, Cook A, Brown NR, Johnson LN, EMBO J. 2005 Feb 9;24(3):452-63. Epub 2005 Jan 20. PMID:15660127
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