2qe2: Difference between revisions
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|PDB= 2qe2 |SIZE=350|CAPTION= <scene name='initialview01'>2qe2</scene>, resolution 2.90Å | |PDB= 2qe2 |SIZE=350|CAPTION= <scene name='initialview01'>2qe2</scene>, resolution 2.90Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=452:2-{[N-(2-ACETYL-5-CHLORO-4-FLUOROPHENYL)GLYCYL]AMINO}BENZOIC ACID'>452</scene> | |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] | |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> | ||
|GENE= ns5b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id= | |GENE= ns5b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31647 Hepatitis C virus subtype 1b]) | ||
|DOMAIN= | |||
|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> | |||
}} | }} | ||
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==About this Structure== | ==About this Structure== | ||
2QE2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/ | 2QE2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_1b Hepatitis c virus subtype 1b]. 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://www.ncbi.nlm.nih.gov/pubmed/17402724 17402724] | 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 | [[Category: Hepatitis c virus subtype 1b]] | ||
[[Category: RNA-directed RNA polymerase]] | [[Category: RNA-directed RNA polymerase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Chopra, R.]] | [[Category: Chopra, R.]] | ||
[[Category: Svenson, K.]] | [[Category: Svenson, K.]] | ||
[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:48:10 2008'' | ||
Revision as of 04:48, 31 March 2008
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| , resolution 2.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | ns5b (Hepatitis C virus subtype 1b) | ||||||
| Activity: | RNA-directed RNA polymerase, with EC number 2.7.7.48 | ||||||
| Related: | 2QE5
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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
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