2cgx

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
[[Image:2cgx.gif|left|200px]]
[[Image:2cgx.gif|left|200px]]
-
{{Structure
+
<!--
-
|PDB= 2cgx |SIZE=350|CAPTION= <scene name='initialview01'>2cgx</scene>, resolution 2.20&Aring;
+
The line below this paragraph, containing "STRUCTURE_2cgx", creates the "Structure Box" on the page.
-
|SITE= <scene name='pdbsite=AC1:3d3+Binding+Site+For+Chain+A'>AC1</scene>
+
You may change the PDB parameter (which sets the PDB file loaded into the applet)
-
|LIGAND= <scene name='pdbligand=3D3:2-[(6-AMINO-7H-PURIN-8-YL)THIO]ACETAMIDE'>3D3</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_2cgx| PDB=2cgx | SCENE= }}
-
|RELATEDENTRY=
+
-
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2cgx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cgx OCA], [http://www.ebi.ac.uk/pdbsum/2cgx PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2cgx RCSB]</span>
+
-
}}
+
'''IDENTIFICATION OF CHEMICALLY DIVERSE CHK1 INHIBITORS BY RECEPTOR-BASED VIRTUAL SCREENING'''
'''IDENTIFICATION OF CHEMICALLY DIVERSE CHK1 INHIBITORS BY RECEPTOR-BASED VIRTUAL SCREENING'''
Line 32: Line 29:
[[Category: Robertson, A G.S.]]
[[Category: Robertson, A G.S.]]
[[Category: Surgenor, A E.]]
[[Category: Surgenor, A E.]]
-
[[Category: atp-binding]]
+
[[Category: Atp-binding]]
-
[[Category: cell cycle]]
+
[[Category: Cell cycle]]
-
[[Category: dna damage]]
+
[[Category: Dna damage]]
-
[[Category: dna repair]]
+
[[Category: Dna repair]]
-
[[Category: docking]]
+
[[Category: Docking]]
-
[[Category: drug design]]
+
[[Category: Drug design]]
-
[[Category: kinase]]
+
[[Category: Kinase]]
-
[[Category: nuclear protein]]
+
[[Category: Nuclear protein]]
-
[[Category: nucleotide-binding]]
+
[[Category: Nucleotide-binding]]
-
[[Category: oncology]]
+
[[Category: Oncology]]
-
[[Category: phosphorylation]]
+
[[Category: Phosphorylation]]
-
[[Category: polymorphism]]
+
[[Category: Polymorphism]]
-
[[Category: serine/threonine-protein kinase]]
+
[[Category: Serine/threonine-protein kinase]]
-
[[Category: transferase]]
+
[[Category: Transferase]]
-
[[Category: ubl conjugation]]
+
[[Category: Ubl conjugation]]
-
[[Category: virtual screening]]
+
[[Category: Virtual screening]]
-
 
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 22:06:46 2008''
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:21:18 2008''
+

Revision as of 19:06, 3 May 2008

Image:2cgx.gif

Template:STRUCTURE 2cgx

IDENTIFICATION OF CHEMICALLY DIVERSE CHK1 INHIBITORS BY RECEPTOR-BASED VIRTUAL SCREENING


Overview

Inhibition of the Chk1 kinase by small molecules is of great therapeutic interest for oncology and in understanding the cellular regulation of the G2/M checkpoint. We report how computational docking of a large electronic catalogue of compounds to an X-ray structure of the Chk1 ATP-binding site allowed prioritisation of a small subset of these compounds for assay. This led to the discovery of 10 novel Chk1 inhibitors, distributed among nine new and clearly different chemical scaffolds. Several of these scaffolds have promising lead-like properties. All these ligands act by competitive binding to the targeted ATP site. The crystal structures of four of these compounds bound to this site are presented, and reasonable modelled docking modes are suggested for the 5 other scaffolds. This structural context is used to assess the potential of these scaffolds for further medicinal chemistry efforts, suggesting that several of them could be elaborated to make additional interactions with the buried part of the ATP site. Some unusual interactions with the conserved kinase backbone motif are pointed out. The ligand-binding modes are also used to discuss their medicinal chemistry potential with respect to undesirable chemical functionalities, whether these functionalities bind directly to the protein or not. Overall, this work illustrates how virtual screening can identify a diverse set of ligands which bind to the targeted site. The structural models for these ligands in the Chk1 ATP-binding site will facilitate further medicinal chemistry efforts targeting this kinase.

About this Structure

2CGX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Identification of chemically diverse Chk1 inhibitors by receptor-based virtual screening., Foloppe N, Fisher LM, Howes R, Potter A, Robertson AG, Surgenor AE, Bioorg Med Chem. 2006 Jul 15;14(14):4792-802. Epub 2006 Mar 29. PMID:16574416 Page seeded by OCA on Sat May 3 22:06:46 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2cgx"
Personal tools