2gc8: Difference between revisions

Revision as of 04:56, 4 May 2008

Structure of a Proline Sulfonamide Inhibitor Bound to HCV NS5b Polymerase

OverviewOverview

Through high throughput screening, substituted proline sulfonamide 6 was identified as HCV NS5b RNA-dependent RNA polymerase inhibitor. Optimization of various regions of the lead molecule resulted in compounds that displayed good potency and selectivity. The crystal structure of 6 and NS5b polymerase complex confirmed the binding near the active site region. The optimization approach and SAR are discussed in detail.

About this StructureAbout this Structure

2GC8 is a Single protein structure of sequence from Hepatitis c virus. Full crystallographic information is available from OCA.

ReferenceReference

Discovery of proline sulfonamides as potent and selective hepatitis C virus NS5b polymerase inhibitors. Evidence for a new NS5b polymerase binding site., Gopalsamy A, Chopra R, Lim K, Ciszewski G, Shi M, Curran KJ, Sukits SF, Svenson K, Bard J, Ellingboe JW, Agarwal A, Krishnamurthy G, Howe AY, Orlowski M, Feld B, O'Connell J, Mansour TS, J Med Chem. 2006 Jun 1;49(11):3052-5. PMID:16722622 Page seeded by OCA on Sun May 4 04:56:26 2008

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

OCA

@@ Line 1: / Line 1: @@
 [[Image:2gc8.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2gc8 |SIZE=350|CAPTION= <scene name='initialview01'>2gc8</scene>, resolution 2.20&Aring;
+The line below this paragraph, containing "STRUCTURE_2gc8", 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=885:1-[(2-AMINO-4-CHLORO-5-METHYLPHENYL)SULFONYL]-L-PROLINE'>885</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=
+-->
-|DOMAIN=
+{{STRUCTURE_2gc8|  PDB=2gc8  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gc8 OCA], [http://www.ebi.ac.uk/pdbsum/2gc8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2gc8 RCSB]</span>
-}}
 '''Structure of a Proline Sulfonamide Inhibitor Bound to HCV NS5b Polymerase'''
@@ Line 42: / Line 39: @@
 [[Category: Sukits, S F.]]
 [[Category: Svenson, K.]]
-[[Category: connell, J O.]]
+[[Category: Connell, J O.]]
-[[Category: transferase]]
+[[Category: Transferase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 04:56:26 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:14:43 2008''