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2iw8
From Proteopedia
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| , resolution 2.30Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE OF HUMAN THR160-PHOSPHO CDK2-CYCLIN A F82H-L83V-H84D MUTANT WITH AN O6-CYCLOHEXYLMETHYLGUANINE INHIBITOR
Overview
Cyclin dependent kinases are a key family of kinases involved in cell cycle regulation and are an attractive target for cancer chemotherapy. The roles of four residues of the cyclin-dependent kinase active site in inhibitor selectivity were investigated by producing cyclin-dependent kinase 2 mutants bearing equivalent cyclin-dependent kinase 4 residues, namely F82H, L83V, H84D, and K89T. Assay of the mutants with a cyclin-dependent kinase 4-selective bisanilinopyrimidine shows that the K89T mutation is primarily responsible for the selectivity of this compound. Use of the cyclin-dependent kinase 2-selective 6-cyclohexylmethoxy-2-(4'-sulfamoylanilino)purine (NU6102) shows that K89T has no role in the selectivity, while the remaining three mutations have a cumulative influence. The results indicate that certain residues that are not frequently considered in structure-aided kinase inhibitor design have an important role to play.
About this Structure
2IW8 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Dissecting the determinants of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 inhibitor selectivity., Pratt DJ, Bentley J, Jewsbury P, Boyle FT, Endicott JA, Noble ME, J Med Chem. 2006 Sep 7;49(18):5470-7. PMID:16942020
Page seeded by OCA on Mon Mar 31 03:49:30 2008
Categories: Homo sapiens | Non-specific serine/threonine protein kinase | Protein complex | Bentley, J. | Boyle, F T. | Endicott, J A. | Jewsbury, P. | Noble, M E.M. | Pratt, D J. | Atp-binding | Cell cycle | Cell cycle complex | Cell division | Cyclin | Kinase | Mitosis | Nucleotide-binding | Phosphorylation | Polymorphism | Serine-threonine-protein kinase | Serine/threonine-protein kinase | Transferase
