2qe2: Difference between revisions

Revision as of 14:47, 4 May 2008

Structure of HCV NS5B Bound to an Anthranilic Acid Inhibitor

OverviewOverview

A series of potent anthranilic acid-based inhibitors of the hepatitis C NS5B polymerase has been identified. The inhibitors bind to a site on NS5B between the thumb and palm regions adjacent to the active site as determined by X-ray crystallography of the enzyme-inhibitor complex. Guided by both molecular modeling and traditional SAR, the enzyme activity of the initial hit was improved by approximately 100-fold, yielding a series of potent and selective NS5B inhibitors with IC50 values as low as 10 nM. These compounds were also inhibitors of the HCV replicon in cultured HUH7 cells.

About this StructureAbout this Structure

2QE2 is a Single protein structure of sequence from Hepatitis c virus subtype 1b. Full crystallographic information is available from OCA.

ReferenceReference

Identification of anthranilic acid derivatives as a novel class of allosteric inhibitors of hepatitis C NS5B polymerase., Nittoli T, Curran K, Insaf S, DiGrandi M, Orlowski M, Chopra R, Agarwal A, Howe AY, Prashad A, Floyd MB, Johnson B, Sutherland A, Wheless K, Feld B, O'Connell J, Mansour TS, Bloom J, J Med Chem. 2007 May 3;50(9):2108-16. Epub 2007 Apr 3. PMID:17402724 Page seeded by OCA on Sun May 4 14:47:51 2008

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

OCA

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 [[Image:2qe2.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2qe2 |SIZE=350|CAPTION= <scene name='initialview01'>2qe2</scene>, resolution 2.90&Aring;
+The line below this paragraph, containing "STRUCTURE_2qe2", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=452:2-{[N-(2-ACETYL-5-CHLORO-4-FLUOROPHENYL)GLYCYL]AMINO}BENZOIC+ACID'>452</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/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= ns5b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31647 Hepatitis C virus subtype 1b])
+-->
-|DOMAIN=
+{{STRUCTURE_2qe2|  PDB=2qe2  |  SCENE=  }}
-|RELATEDENTRY=[[2qe5|2QE5]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qe2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qe2 OCA], [http://www.ebi.ac.uk/pdbsum/2qe2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qe2 RCSB]</span>
-}}
 '''Structure of HCV NS5B Bound to an Anthranilic Acid Inhibitor'''
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 [[Category: Chopra, R.]]
 [[Category: Svenson, K.]]
-[[Category: transferase]]
+[[Category: Transferase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 14:47:51 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:48:10 2008''