2GC8

Structure of a Proline Sulfonamide Inhibitor Bound to HCV NS5b Polymerase

Summary for 2GC8

• Entry DOI: 10.2210/pdb2gc8/pdb
• Descriptor: RNA-directed RNA polymerase, 1-[(2-AMINO-4-CHLORO-5-METHYLPHENYL)SULFONYL]-L-PROLINE (3 entities in total)
• Functional Keywords: transferase
• Biological source: Hepatitis C virus
• Total number of polymer chains: 2
• Total formula weight: 129132.75

Authors

Gopalsamy, A.,Chopra, R.,Lim, K.,Ciszewski, G.,Shi, M.,Curran, K.J.,Sukits, S.F.,Svenson, K.,Bard, J.,Ellingboe, J.W.,Agarwal, A.,Krishnamurthy, G.,Howe, A.Y.,Orlowski, M.,Feld, B.,O'connell, J.,Mansour, T.S. (deposition date: 2006-03-13, release date: 2006-06-13, Last modification date: 2023-08-30)

Primary citation

Gopalsamy, A.,Chopra, R.,Lim, K.,Ciszewski, G.,Shi, M.,Curran, K.J.,Sukits, S.F.,Svenson, K.,Bard, J.,Ellingboe, J.W.,Agarwal, A.,Krishnamurthy, G.,Howe, A.Y.,Orlowski, M.,Feld, B.,O'connell, J.,Mansour, T.S.
Discovery of Proline Sulfonamides as Potent and Selective Hepatitis C Virus NS5b Polymerase Inhibitors. Evidence for a New NS5b Polymerase Binding Site.
J.Med.Chem., 49:3052-3055, 2006

PubMed Abstract: 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.

PubMed: 16722622
DOI: 10.1021/jm060168g

Experimental method

X-RAY DIFFRACTION (2.2 Å)