View source for 1oi9

[[Image:1oi9.gif|left|200px]]<br /><applet load="1oi9" size="350" color="white" frame="true" align="right" spinBox="true" 
caption="1oi9, resolution 2.100&Aring;" />
'''STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/CYCLIN A COMPLEXED WITH A 6-CYCLOHEXYLMETHYLOXY-2-ANILINO-PURINE INHIBITOR'''<br />

==Overview==
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 Structure==
1OI9 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 <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=N20:'>N20</scene> and <scene name='pdbligand=SGM:'>SGM</scene> 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] Known structural/functional Site: <scene name='pdbsite=AC1:Sgm+Binding+Site+For+Chain+D'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OI9 OCA]. 

==Reference==
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://ispc.weizmann.ac.il//pmbin/getpm?pmid=15239650 15239650]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Transferred entry: 2.7.11.1]]
[[Category: Endicott, J.A.]]
[[Category: Noble, M.E.M.]]
[[Category: Pratt, D.J.]]
[[Category: MG]]
[[Category: N20]]
[[Category: SGM]]
[[Category: atp-binding]]
[[Category: cell cycle]]
[[Category: cell division]]
[[Category: kinase]]
[[Category: mitosis]]
[[Category: phosphorylation]]
[[Category: serine/threonine-protein kinase]]
[[Category: transferase]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 09:58:26 2008''