1H24

CDK2/CyclinA in complex with a 9 residue recruitment peptide from E2F

Summary for 1H24

• Entry DOI: 10.2210/pdb1h24/pdb
• Related: 1AQ1 1B38 1B39 1BUH 1CKP 1DI8 1DM2 1E1V 1E1X 1F5Q 1FIN 1FQ1 1FVT 1FVV 1G5S 1GIH 1GII 1GIJ 1GY3 1GZ8 1H00 1H01 1H06 1H07 1H08 1H0U 1H0V 1H0W 1H1P 1H1Q 1H1R 1H1S 1H25 1H26 1H27 1HCK 1HCL 1JST 1JSU 1JSV 1JVP 1KE5 1KE6 1KE7 1KE8 1KE9 1QMZ
• Descriptor: CELL DIVISION PROTEIN KINASE 2, CYCLIN A2, TRANSCRIPTION FACTOR E2F1, ... (4 entities in total)
• Functional Keywords: transferase, cell cycle, protein kinase, cyclin, cdk2, recruitment, peptide specificity, serine/threonine-protein kinase, atp- binding, cell division, mitosis, phosphorylation
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus: P20248 Q01094
• Total number of polymer chains: 5
• Total formula weight: 129571.02

Authors

Tews, I.,Cheng, K.Y.,Lowe, E.D.,Noble, M.E.M.,Brown, N.R.,Gul, S.,Gamblin, S.,Johnson, L.N. (deposition date: 2002-07-31, release date: 2003-02-01, Last modification date: 2024-10-23)

Primary citation

Lowe, E.D.,Tews, I.,Cheng, K.Y.,Brown, N.R.,Gul, S.,Noble, M.E.M.,Gamblin, S.,Johnson, L.N.
Specificity Determinants of Recruitment Peptides Bound to Phospho-Cdk2/Cyclin A
Biochemistry, 41:15625-, 2002

PubMed Abstract: 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.

PubMed: 12501191
DOI: 10.1021/BI0268910

Experimental method

X-RAY DIFFRACTION (2.5 Å)