2uzd: Difference between revisions

Revision as of 17:52, 4 May 2008

CRYSTAL STRUCTURE OF HUMAN CDK2 COMPLEXED WITH A THIAZOLIDINONE INHIBITOR

OverviewOverview

Virtual screening against a pCDK2/cyclin A crystal structure led to the identification of a potent and novel CDK2 inhibitor, which exhibited an unusual mode of interaction with the kinase binding motif. With the aid of X-ray crystallography and modelling, a medicinal chemistry strategy was implemented to probe the interactions seen in the crystal structure and to establish SAR. A fragment-based approach was also considered but a different, more conventional, binding mode was observed. Compound selectivity against GSK-3beta was improved using a rational design strategy, with crystallographic verification of the CDK2 binding mode.

About this StructureAbout this Structure

2UZD is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Discovery of a potent CDK2 inhibitor with a novel binding mode, using virtual screening and initial, structure-guided lead scoping., Richardson CM, Nunns CL, Williamson DS, Parratt MJ, Dokurno P, Howes R, Borgognoni J, Drysdale MJ, Finch H, Hubbard RE, Jackson PS, Kierstan P, Lentzen G, Moore JD, Murray JB, Simmonite H, Surgenor AE, Torrance CJ, Bioorg Med Chem Lett. 2007 Jul 15;17(14):3880-5. Epub 2007 May 6. PMID:17570665 Page seeded by OCA on Sun May 4 17:52:04 2008

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

OCA

@@ Line 1: / Line 1: @@
 [[Image:2uzd.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2uzd |SIZE=350|CAPTION= <scene name='initialview01'>2uzd</scene>, resolution 2.72&Aring;
+The line below this paragraph, containing "STRUCTURE_2uzd", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:C85+Binding+Site+For+Chain+C'>AC1</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=C85:4-{5-[(Z)-(2-IMINO-4-OXO-1,3-THIAZOLIDIN-5-YLIDENE)METHYL]FURAN-2-YL}BENZENESULFONAMIDE'>C85</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY=
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_2uzd|  PDB=2uzd  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2uzd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uzd OCA], [http://www.ebi.ac.uk/pdbsum/2uzd PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2uzd RCSB]</span>
-}}
 '''CRYSTAL STRUCTURE OF HUMAN CDK2 COMPLEXED WITH A THIAZOLIDINONE INHIBITOR'''
@@ Line 29: / Line 26: @@
 [[Category: Richardson, C M.]]
 [[Category: Surgenor, A E.]]
-[[Category: atp-binding]]
+[[Category: Atp-binding]]
-[[Category: cdk2]]
+[[Category: Cdk2]]
-[[Category: cell cycle]]
+[[Category: Cell cycle]]
-[[Category: cell division]]
+[[Category: Cell division]]
-[[Category: cyclin]]
+[[Category: Cyclin]]
-[[Category: kinase]]
+[[Category: Kinase]]
-[[Category: mitosis]]
+[[Category: Mitosis]]
-[[Category: nucleotide- binding]]
+[[Category: Nucleotide- binding]]
-[[Category: phosphorylation]]
+[[Category: Phosphorylation]]
-[[Category: serine/threonine-protein kinase]]
+[[Category: Serine/threonine-protein kinase]]
-[[Category: thiazolidinone ligand]]
+[[Category: Thiazolidinone ligand]]
-[[Category: transferase]]
+[[Category: Transferase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 17:52:04 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:06:35 2008''