2gc8
| |||||||
| , resolution 2.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | RNA-directed RNA polymerase, with EC number 2.7.7.48 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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
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