2qe5: Difference between revisions

Revision as of 19:38, 21 February 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

2QE5 is a Single protein structure of sequence from Hepatitis c virus subtype 3b with as ligand. Active as RNA-directed RNA polymerase, with EC number 2.7.7.48 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 Thu Feb 21 18:38:37 2008

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 ==Overview==
-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.
+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 Structure==
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 [[Category: transferase polymerase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:21:07 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:38:37 2008''