2iw8
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Cyclin dependent kinases are a key family of kinases involved in cell | + | 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== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Transferred entry: 2 | + | [[Category: Transferred entry: 2 7.11 1]] |
[[Category: Bentley, J.]] | [[Category: Bentley, J.]] | ||
| - | [[Category: Boyle, F | + | [[Category: Boyle, F T.]] |
| - | [[Category: Endicott, J | + | [[Category: Endicott, J A.]] |
[[Category: Jewsbury, P.]] | [[Category: Jewsbury, P.]] | ||
| - | [[Category: Noble, M | + | [[Category: Noble, M E.M.]] |
| - | [[Category: Pratt, D | + | [[Category: Pratt, D J.]] |
[[Category: 4SP]] | [[Category: 4SP]] | ||
[[Category: SGM]] | [[Category: SGM]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:56:39 2008'' |
Revision as of 15:56, 21 February 2008
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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 with and as ligands. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Known structural/functional Site: . 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 Thu Feb 21 17:56:39 2008
Categories: Homo sapiens | Protein complex | Transferred entry: 2 7.11 1 | Bentley, J. | Boyle, F T. | Endicott, J A. | Jewsbury, P. | Noble, M E.M. | Pratt, D J. | 4SP | SGM | 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
