2W9Z

Crystal Structure of CDK4 in complex with a D-type cyclin

Summary for 2W9Z

• Entry DOI: 10.2210/pdb2w9z/pdb
• Related: 1LD2 2W96 2W99 2W9F
• Descriptor: G1/S-SPECIFIC CYCLIN-D1, CELL DIVISION PROTEIN KINASE 4 (3 entities in total)
• Functional Keywords: transferase, cyclin dependent kinase, transferase oncology, cell cycle, drug design
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 2
• Total formula weight: 63820.93

Authors

Day, P.J.,Cleasby, A.,Tickle, I.J.,Reilly, M.O.,Coyle, J.E.,Holding, F.P.,McMenamin, R.L.,Yon, J.,Chopra, R.,Lengauer, C.,Jhoti, H. (deposition date: 2009-01-30, release date: 2009-03-10, Last modification date: 2023-12-13)

Primary citation

Day, P.J.,Cleasby, A.,Tickle, I.J.,O'Reilly, M.,Coyle, J.E.,Holding, F.P.,Mcmenamin, R.L.,Yon, J.,Chopra, R.,Lengauer, C.,Jhoti, H.
Crystal Structure of Human Cdk4 in Complex with a D-Type Cyclin.
Proc.Natl.Acad.Sci.USA, 106:4166-, 2009

PubMed Abstract: The cyclin D1-cyclin-dependent kinase 4 (CDK4) complex is a key regulator of the transition through the G(1) phase of the cell cycle. Among the cyclin/CDKs, CDK4 and cyclin D1 are the most frequently activated by somatic genetic alterations in multiple tumor types. Thus, aberrant regulation of the CDK4/cyclin D1 pathway plays an essential role in oncogenesis; hence, CDK4 is a genetically validated therapeutic target. Although X-ray crystallographic structures have been determined for various CDK/cyclin complexes, CDK4/cyclin D1 has remained highly refractory to structure determination. Here, we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A. Although CDK4 is bound to cyclin D1 and has a phosphorylated T-loop, CDK4 is in an inactive conformation and the conformation of the heterodimer diverges from the previously known CDK/cyclin binary complexes, which suggests a unique mechanism for the process of CDK4 regulation and activation.

PubMed: 19237565
DOI: 10.1073/PNAS.0809645106

Experimental method

X-RAY DIFFRACTION (2.45 Å)