1ogu: Difference between revisions

Revision as of 03:49, 3 May 2008

STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/CYCLIN A COMPLEXED WITH A 2-ARYLAMINO-4-CYCLOHEXYLMETHYL-5-NITROSO-6-AMINOPYRIMIDINE INHIBITOR

OverviewOverview

A series of O(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines bearing 2-arylamino substituents was synthesised and evaluated for CDK1 and CDK2 inhibitory activity. Consistent with analogous studies with O(6)-cyclohexylmethylpurines, 2-arylaminopyrimidines with a sulfonamide or carboxamide group at the 4'-position were potent inhibitors, with IC(50) values against CDK2 of 1.1+/-0.3 and 34+/-8 nM, respectively. The crystal structure of the 4'-carboxamide derivative, in complex with phospho-Thr160 CDK2/cyclin A, confirmed the expected binding mode of the inhibitor, and revealed an additional interaction between the carboxamide function and an aspartate residue.

About this StructureAbout this Structure

1OGU is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2., Sayle KL, Bentley J, Boyle FT, Calvert AH, Cheng Y, Curtin NJ, Endicott JA, Golding BT, Hardcastle IR, Jewsbury P, Mesguiche V, Newell DR, Noble ME, Parsons RJ, Pratt DJ, Wang LZ, Griffin RJ, Bioorg Med Chem Lett. 2003 Sep 15;13(18):3079-82. PMID:12941338 Page seeded by OCA on Sat May 3 03:49:45 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1ogu.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1ogu |SIZE=350|CAPTION= <scene name='initialview01'>1ogu</scene>, resolution 2.60&Aring;
+The line below this paragraph, containing "STRUCTURE_1ogu", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:Sgm+Binding+Site+For+Chain+D'>AC1</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=SGM:MONOTHIOGLYCEROL'>SGM</scene>, <scene name='pdbligand=ST8:4-{[4-AMINO-6-(CYCLOHEXYLMETHOXY)-5-NITROSOPYRIMIDIN-2-YL]AMINO}BENZAMIDE'>ST8</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|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>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1ogu|  PDB=1ogu  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ogu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ogu OCA], [http://www.ebi.ac.uk/pdbsum/1ogu PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ogu RCSB]</span>
-}}
 '''STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/CYCLIN A COMPLEXED WITH A 2-ARYLAMINO-4-CYCLOHEXYLMETHYL-5-NITROSO-6-AMINOPYRIMIDINE INHIBITOR'''
@@ Line 29: / Line 26: @@
 [[Category: Noble, M E.M.]]
 [[Category: Pratt, D J.]]
-[[Category: atp-binding]]
+[[Category: Atp-binding]]
-[[Category: cell cycle]]
+[[Category: Cell cycle]]
-[[Category: cell division]]
+[[Category: Cell division]]
-[[Category: kinase]]
+[[Category: Kinase]]
-[[Category: mitosis]]
+[[Category: Mitosis]]
-[[Category: phosphorylation]]
+[[Category: Phosphorylation]]
-[[Category: serine/threonine-protein kinase]]
+[[Category: Serine/threonine-protein kinase]]
-[[Category: transferase]]
+[[Category: Transferase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 03:49:45 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:45:04 2008''