2qe2
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:2qe2.jpg|left|200px]] | + | [[Image:2qe2.jpg|left|200px]] |
| - | + | ||
| - | '''Structure of HCV NS5B Bound to an Anthranilic Acid Inhibitor''' | + | {{Structure |
| + | |PDB= 2qe2 |SIZE=350|CAPTION= <scene name='initialview01'>2qe2</scene>, resolution 2.90Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=452:2-{[N-(2-ACETYL-5-CHLORO-4-FLUOROPHENYL)GLYCYL]AMINO}BENZOIC ACID'>452</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= ns5b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=42791 Hepatitis C virus subtype 3b]) | ||
| + | }} | ||
| + | |||
| + | '''Structure of HCV NS5B Bound to an Anthranilic Acid Inhibitor''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2QE2 is a [ | + | 2QE2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_3b Hepatitis c virus subtype 3b]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QE2 OCA]. |
==Reference== | ==Reference== | ||
| - | 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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17402724 17402724] |
[[Category: Hepatitis c virus subtype 3b]] | [[Category: Hepatitis c virus subtype 3b]] | ||
[[Category: RNA-directed RNA polymerase]] | [[Category: RNA-directed RNA polymerase]] | ||
| Line 20: | Line 29: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:24:48 2008'' |
Revision as of 16:24, 20 March 2008
| |||||||
| , resolution 2.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | ns5b (Hepatitis C virus subtype 3b) | ||||||
| Activity: | RNA-directed RNA polymerase, with EC number 2.7.7.48 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of HCV NS5B Bound to an Anthranilic Acid Inhibitor
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.
About this Structure
2QE2 is a Single protein structure of sequence from Hepatitis c virus subtype 3b. Full crystallographic information is available from OCA.
Reference
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 Mar 20 18:24:48 2008
