2C5V

Differential Binding Of Inhibitors To Active And Inactive Cdk2 Provides Insights For Drug Design

Replaces:  1OKU

Summary for 2C5V

• Entry DOI: 10.2210/pdb2c5v/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 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 1W98 1WCC 1Y8Y 1Y91 2B52 2B53 2B54 2B55 2BHE 2BHH 2BKZ 2BPM 2BTR 2BTS 2C4G 2C5N 2C5O 2C5P 2C5T 2C5X 2C5Y 2C68 2C69
• Descriptor: CELL DIVISION PROTEIN KINASE 2, CYCLIN A2, ALA-ALA-ABA-ARG-SER-LEU-ILE-PFF-NH2, ... (5 entities in total)
• Functional Keywords: atp-binding, cell cycle, cell division, complex (kinase-cyclin), cycin a, cyclin, drug design, ligand exchange, kinase, mitosis, nucleotide-binding, phosphorylation, serine/threonine-protein kinase, transferase, complex (transferase-cyclin)
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: P24941; Nucleus : P20248
• Total number of polymer chains: 6
• Total formula weight: 129918.59

Authors

Kontopidis, G.,McInnes, C.,Pandalaneni, S.R.,McNae, I.,Gibson, D.,Mezna, M.,Thomas, M.,Wood, G.,Wang, S.,Walkinshaw, M.D.,Fischer, P.M. (deposition date: 2005-11-02, release date: 2006-03-01, Last modification date: 2023-12-13)

Primary citation

Kontopidis, G.,Mcinnes, C.,Pandalaneni, S.R.,Mcnae, I.,Gibson, D.,Mezna, M.,Thomas, M.,Wood, G.,Wang, S.,Walkinshaw, M.D.,Fischer, P.M.
Differential Binding of Inhibitors to Active and Inactive Cdk2 Provides Insights for Drug Design.
Chem.Biol., 13:201-, 2006

PubMed Abstract: The cyclin-dependent kinases (CDKs) have been characterized in complex with a variety of inhibitors, but the majority of structures solved are in the inactive form. We have solved the structures of six inhibitors in both the monomeric CDK2 and binary CDK2/cyclinA complexes and demonstrate that significant differences in ligand binding occur depending on the activation state. The binding mode of two ligands in particular varies substantially in active and inactive CDK2. Furthermore, energetic analysis of CDK2/cyclin/inhibitors demonstrates that a good correlation exists between the in vitro potency and the calculated energies of interaction, but no such relationship exists for CDK2/inhibitor structures. These results confirm that monomeric CDK2 ligand complexes do not fully reflect active conformations, revealing significant implications for inhibitor design while also suggesting that the monomeric CDK2 conformation can be selectively inhibited.

PubMed: 16492568
DOI: 10.1016/J.CHEMBIOL.2005.11.011

Experimental method

X-RAY DIFFRACTION (2.9 Å)