1W98

The structural basis of CDK2 activation by cyclin E

Summary for 1W98

• Entry DOI: 10.2210/pdb1w98/pdb
• Related: 1AQ1 1B38 1B39 1BUH 1CKP 1DI8 1DM2 1E1V 1E1X 1E9H 1F5Q 1FIN 1FQ1 1FVT 1FVV 1G5S 1GIH 1GII 1GIJ 1GY3 1GZ8 1H00 1H01 1H07 1H08 1H0V 1H0W 1H1P 1H1Q 1H1R 1H1S 1H24 1H25 1H26 1H27 1H28 1HCK 1HCL 1JST 1JSU 1JSV 1JVP 1KE5 1KE6 1KE7 1KE8 1KE9 1OGU 1OI9 1OIQ 1OIR 1OIT 1OIU 1OIY 1OKU 1OKV 1OKW 1OL1 1OL2 1P2A 1P5E 1PF8 1PKD 1PW2 1PXI 1PXJ 1PXK 1PXL 1PXM 1PXN 1PXO 1PXP 1PYE 1QMZ 1R78 1URC 1URW 1V1K 1VYW 1VYZ 1W0X 1W8C
• Descriptor: CELL DIVISION PROTEIN KINASE 2, G1/S-SPECIFIC CYCLIN E1 (3 entities in total)
• Functional Keywords: cell cycle, transferase
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus: P24864
• Total number of polymer chains: 2
• Total formula weight: 66939.76

Authors

Lowe, E.D.,Honda, R.,Dubinina, E.,Skamnaki, V.,Cook, A.,Johnson, L.N. (deposition date: 2004-10-07, release date: 2005-02-02, Last modification date: 2024-10-23)

Primary citation

Honda, R.,Lowe, E.D.,Dubinina, E.,Skamnaki, V.,Cook, A.,Brown, N.,Johnson, L.N.
The Structure of Cyclin E1/Cdk2: Implications for Cdk2 Activation and Cdk2-Independent Roles
Embo J., 24:452-, 2005

PubMed Abstract: 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.

PubMed: 15660127
DOI: 10.1038/SJ.EMBOJ.7600554

Experimental method

X-RAY DIFFRACTION (2.15 Å)