2c5n: Difference between revisions

Revision as of 21:17, 3 May 2008

DIFFERENTIAL BINDING OF INHIBITORS TO ACTIVE AND INACTIVE CDK2 PROVIDES INSIGHTS FOR DRUG DESIGN

OverviewOverview

The cyclin-dependent kinases (CDKs) have been characterized in complex with a variety of inhibitors, but the majority of structures solved are in the inactive form. We have solved the structures of six inhibitors in both the monomeric CDK2 and binary CDK2/cyclinA complexes and demonstrate that significant differences in ligand binding occur depending on the activation state. The binding mode of two ligands in particular varies substantially in active and inactive CDK2. Furthermore, energetic analysis of CDK2/cyclin/inhibitors demonstrates that a good correlation exists between the in vitro potency and the calculated energies of interaction, but no such relationship exists for CDK2/inhibitor structures. These results confirm that monomeric CDK2 ligand complexes do not fully reflect active conformations, revealing significant implications for inhibitor design while also suggesting that the monomeric CDK2 conformation can be selectively inhibited.

About this StructureAbout this Structure

2C5N is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Differential binding of inhibitors to active and inactive CDK2 provides insights for drug design., Kontopidis G, McInnes C, Pandalaneni SR, McNae I, Gibson D, Mezna M, Thomas M, Wood G, Wang S, Walkinshaw MD, Fischer PM, Chem Biol. 2006 Feb;13(2):201-11. PMID:16492568 Page seeded by OCA on Sat May 3 21:17:25 2008

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

OCA

@@ Line 1: / Line 1: @@
 [[Image:2c5n.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2c5n |SIZE=350|CAPTION= <scene name='initialview01'>2c5n</scene>, resolution 2.10&Aring;
+The line below this paragraph, containing "STRUCTURE_2c5n", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:Ck8+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=CK8:N-[4-(2,4-DIMETHYL-THIAZOL-5-YL)-PYRIMIDIN-2-YL]-N&#39;,N&#39;-DIMETHYL-BENZENE-1,4-DIAMINE'>CK8</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_2c5n|  PDB=2c5n  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2c5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c5n OCA], [http://www.ebi.ac.uk/pdbsum/2c5n PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2c5n RCSB]</span>
-}}
 '''DIFFERENTIAL BINDING OF INHIBITORS TO ACTIVE AND INACTIVE CDK2 PROVIDES INSIGHTS FOR DRUG DESIGN'''
@@ Line 37: / Line 34: @@
 [[Category: Wang, S.]]
 [[Category: Wood, G.]]
-[[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: differential inhibition]]
+[[Category: Differential inhibition]]
-[[Category: kinase]]
+[[Category: Kinase]]
-[[Category: mitosis]]
+[[Category: Mitosis]]
-[[Category: nucleotide-binding]]
+[[Category: Nucleotide-binding]]
-[[Category: phosphorylation]]
+[[Category: Phosphorylation]]
-[[Category: polymorphism]]
+[[Category: Polymorphism]]
-[[Category: serine/threonine-protein]]
+[[Category: Serine/threonine-protein]]
-[[Category: transferase]]
+[[Category: Transferase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 21:17:25 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:16:42 2008''