1w98
From Proteopedia
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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
Page seeded by OCA on Mon Nov 12 19:48:12 2007
