1oi9: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 1oi9 |SIZE=350|CAPTION= <scene name='initialview01'>1oi9</scene>, resolution 2.100Å | |PDB= 1oi9 |SIZE=350|CAPTION= <scene name='initialview01'>1oi9</scene>, resolution 2.100Å | ||
|SITE= <scene name='pdbsite=AC1:Sgm+Binding+Site+For+Chain+D'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Sgm+Binding+Site+For+Chain+D'>AC1</scene> | ||
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=N20:6-CYCLOHEXYLMETHYLOXY-2-(4'-HYDROXYANILINO)PURINE'>N20</scene> | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=N20:6-CYCLOHEXYLMETHYLOXY-2-(4'-HYDROXYANILINO)PURINE'>N20</scene>, <scene name='pdbligand=SGM:MONOTHIOGLYCEROL'>SGM</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/ | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1oi9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oi9 OCA], [http://www.ebi.ac.uk/pdbsum/1oi9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1oi9 RCSB]</span> | |||
}} | }} | ||
| Line 21: | Line 24: | ||
N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2., Hardcastle IR, Arris CE, Bentley J, Boyle FT, Chen Y, Curtin NJ, Endicott JA, Gibson AE, Golding BT, Griffin RJ, Jewsbury P, Menyerol J, Mesguiche V, Newell DR, Noble ME, Pratt DJ, Wang LZ, Whitfield HJ, J Med Chem. 2004 Jul 15;47(15):3710-22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15239650 15239650] | N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2., Hardcastle IR, Arris CE, Bentley J, Boyle FT, Chen Y, Curtin NJ, Endicott JA, Gibson AE, Golding BT, Griffin RJ, Jewsbury P, Menyerol J, Mesguiche V, Newell DR, Noble ME, Pratt DJ, Wang LZ, Whitfield HJ, J Med Chem. 2004 Jul 15;47(15):3710-22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15239650 15239650] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | |||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Endicott, J A.]] | [[Category: Endicott, J A.]] | ||
[[Category: Noble, M E.M.]] | [[Category: Noble, M E.M.]] | ||
[[Category: Pratt, D J.]] | [[Category: Pratt, D J.]] | ||
[[Category: atp-binding]] | [[Category: atp-binding]] | ||
[[Category: cell cycle]] | [[Category: cell cycle]] | ||
| Line 38: | Line 38: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:45:43 2008'' | ||
Revision as of 22:45, 30 March 2008
| |||||||
| , resolution 2.100Å | |||||||
|---|---|---|---|---|---|---|---|
| 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 COMPLEXED WITH A 6-CYCLOHEXYLMETHYLOXY-2-ANILINO-PURINE INHIBITOR
OverviewOverview
The adenosine 5'-triphosphate (ATP) competitive cyclin-dependent kinase inhibitor O(6)-cyclohexylmethylguanine (NU2058, 1) has been employed as the lead in a structure-based drug discovery program resulting in the discovery of the potent CDK1 and -2 inhibitor NU6102 (3, IC(50) = 9.5 nM and 5.4 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively). The SAR for this series have been explored further by the synthesis and evaluation of 45 N(2)-substituted analogues of NU2058. These studies have confirmed the requirement for the hydrogen bonding N(2)-NH group and the requirement for an aromatic N(2)-substituent to confer potency in the series. Additional potency is conferred by the presence of a group capable of donating a hydrogen bond at the 4'-position, for example, the 4'-hydroxy derivative (25, IC(50) = 94 nM and 69 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively), 4'-monomethylsulfonamide derivative (28, IC(50) = 9 nM and 7.0 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively), and 4'-carboxamide derivative (34, IC(50) = 67 nM and 64 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively). X-ray crystal structures have been obtained for key compounds and have been used to explain the observed trends in activity.
About this StructureAbout this Structure
1OI9 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2., Hardcastle IR, Arris CE, Bentley J, Boyle FT, Chen Y, Curtin NJ, Endicott JA, Gibson AE, Golding BT, Griffin RJ, Jewsbury P, Menyerol J, Mesguiche V, Newell DR, Noble ME, Pratt DJ, Wang LZ, Whitfield HJ, J Med Chem. 2004 Jul 15;47(15):3710-22. PMID:15239650
Page seeded by OCA on Sun Mar 30 22:45:43 2008