2iw9: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
==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== | ||
| Line 13: | Line 13: | ||
[[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: MG]] | [[Category: MG]] | ||
| Line 37: | Line 37: | ||
[[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
|
STRUCTURE OF HUMAN THR160-PHOSPHO CDK2-CYCLIN A COMPLEXED WITH A BISANILINOPYRIMIDINE 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
2IW9 is a Protein complex structure of sequences from Homo sapiens with MG, 4SP and SGM as ligands. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Known structural/functional Site: AC1. 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
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- 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
- MG
- 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
