2iw8
From Proteopedia
| Line 5: | Line 5: | ||
==Overview== | ==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. . | + | 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== | ||
| - | 2IW8 is a | + | 2IW8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with 4SP and SGM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.1 Transferred entry: 2.7.11.1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.37 2.7.1.37] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2IW8 OCA]. |
==Reference== | ==Reference== | ||
| Line 37: | Line 37: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:23:59 2007'' |
Revision as of 11:18, 5 November 2007
|
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 4SP and SGM as ligands. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Structure known Active 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 Mon Nov 5 13:23:59 2007
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
