5HQ0

Ternary complex of human proteins CDK1, Cyclin B and CKS2, bound to an inhibitor

Summary for 5HQ0

• Entry DOI: 10.2210/pdb5hq0/pdb
• Descriptor: Cyclin-dependent kinase 1, G2/mitotic-specific cyclin-B1, Cyclin-dependent kinases regulatory subunit 2, ... (5 entities in total)
• Functional Keywords: cdk1, cyclin b, cks2, cell-cycle, protein kinase, inhibitor, transferase
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus: P06493; Cytoplasm: P14635
• Total number of polymer chains: 3
• Total formula weight: 76574.67

Authors

Noble, M.E.,Martin, M.P.,Korolchuk, S.,Brown, N.R.,Moukhametzianov, R.,Stanley, W.A. (deposition date: 2016-01-21, release date: 2016-03-02, Last modification date: 2024-05-08)

Primary citation

Brown, N.R.,Korolchuk, S.,Martin, M.P.,Stanley, W.A.,Moukhametzianov, R.,Noble, M.E.,Endicott, J.A.
CDK1 structures reveal conserved and unique features of the essential cell cycle CDK.
Nat Commun, 6:6769-, 2015

PubMed Abstract: CDK1 is the only essential cell cycle CDK in human cells and is required for successful completion of M-phase. It is the founding member of the CDK family and is conserved across all eukaryotes. Here we report the crystal structures of complexes of CDK1-Cks1 and CDK1-cyclin B-Cks2. These structures confirm the conserved nature of the inactive monomeric CDK fold and its ability to be remodelled by cyclin binding. Relative to CDK2-cyclin A, CDK1-cyclin B is less thermally stable, has a smaller interfacial surface, is more susceptible to activation segment dephosphorylation and shows differences in the substrate sequence features that determine activity. Both CDK1 and CDK2 are potential cancer targets for which selective compounds are required. We also describe the first structure of CDK1 bound to a potent ATP-competitive inhibitor and identify aspects of CDK1 structure and plasticity that might be exploited to develop CDK1-selective inhibitors.

PubMed: 25864384
DOI: 10.1038/ncomms7769

Experimental method

X-RAY DIFFRACTION (2.3 Å)