3QGH

Crystal structure of the hepatitis C virus NS5B RNA-dependent RNA polymerase genotype 1a complex with N-cyclopropyl-6-[(3R)-3-{[4-(trifluoromethoxy)benzyl]carbamoyl}-4-{[4-(trifluoromethoxy)phenyl]sulfonyl}piperazin-1-yl]pyridazine-3-carboxamide

Summary for 3QGH

• Entry DOI: 10.2210/pdb3qgh/pdb
• Related: 3QGD 3QGE 3QGF 3QGG 3QGI
• Descriptor: RNA-directed RNA polymerase, N-cyclopropyl-6-[(3R)-3-{[4-(trifluoromethoxy)benzyl]carbamoyl}-4-{[4-(trifluoromethoxy)phenyl]sulfonyl}piperazin-1-yl]pyridazine-3-carboxamide, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: ns5b, polymerase, hcv, fingers, palm, thumb, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Hepatitis C virus subtype 1a
• Total number of polymer chains: 1
• Total formula weight: 64181.77

Authors

Sheriff, S. (deposition date: 2011-01-24, release date: 2011-04-20, Last modification date: 2023-09-13)

Primary citation

Gentles, R.G.,Sheriff, S.,Beno, B.R.,Wan, C.,Kish, K.,Ding, M.,Zheng, X.,Chupak, L.,Poss, M.A.,Witmer, M.R.,Morin, P.,Wang, Y.K.,Rigat, K.,Lemm, J.,Voss, S.,Liu, M.,Pelosi, L.,Roberts, S.B.,Gao, M.,Kadow, J.F.
Investigation of the mode of binding of a novel series of N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamides to the hepatitis C virus polymerase.
Bioorg.Med.Chem.Lett., 21:2212-2215, 2011

PubMed Abstract: Structure based rationales for the activities of potent N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamide inhibitors of the hepatitis C viral polymerase are described herein. These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and co-crystal structures of select examples from this series with NS5B are reported. Comparison of co-crystal structures of a potent analog with both NS5B genotype 1a and genotype 1b provides a possible explanation for the genotype-selectivity observed with this compound class and suggests opportunities for the further optimization of the series.

PubMed: 21441029
DOI: 10.1016/j.bmcl.2011.03.011

Experimental method

X-RAY DIFFRACTION (2.14 Å)