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2w96
From Proteopedia
| 2w96, resolution 2.30Å () | |||||||||
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| Activity: | Cyclin-dependent kinase, with EC number 2.7.11.22 | ||||||||
| Related: | 1ld2, 2w99, 2w9z, 2w9f | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
CRYSTAL STRUCTURE OF CDK4 IN COMPLEX WITH A D-TYPE CYCLIN
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.
Crystal structure of human CDK4 in complex with a D-type cyclin., Day PJ, Cleasby A, Tickle IJ, O'Reilly M, Coyle JE, Holding FP, McMenamin RL, Yon J, Chopra R, Lengauer C, Jhoti H, Proc Natl Acad Sci U S A. 2009 Feb 23. PMID:19237565
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2W96 is a 2 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Day PJ, Cleasby A, Tickle IJ, O'Reilly M, Coyle JE, Holding FP, McMenamin RL, Yon J, Chopra R, Lengauer C, Jhoti H. Crystal structure of human CDK4 in complex with a D-type cyclin. Proc Natl Acad Sci U S A. 2009 Feb 23. PMID:19237565
Page seeded by OCA on Thu Apr 2 16:20:56 2009
Categories: Cyclin-dependent kinase | Homo sapiens | Chopra, R. | Cleasby, A. | Coyle, J E. | Day, P J. | Holding, F P. | Jhoti, H. | Lengauer, C. | Mcmenamin, R L. | Reilly, M O. | Tickle, I J. | Yon, J. | Atp-binding | Cell cycle | Cell division | Chromosomal rearrangement | Cyclin | Cyclin dependent kinase | Disease mutation | Drug desgn | Kinase | Nucleotide-binding | Oncology | Phosphoprotein | Polymorphism | Proto-oncogene | Serine/threonine-protein kinase | Transferase
