1NHV

Hepatitis C virus RNA polymerase in complex with non-nucleoside analogue inhibitor

Summary for 1NHV

• Entry DOI: 10.2210/pdb1nhv/pdb
• Descriptor: HEPATITIS C VIRUS NS5B RNA-DEPENDENT RNA POLYMERASE, (2S)-2-[(5-BENZOFURAN-2-YL-THIOPHEN-2-YLMETHYL)-(2,4-DICHLORO-BENZOYL)-AMINO]-3-PHENYL-PROPIONIC ACID (2 entities in total)
• Functional Keywords: hepatitis c; rna polymerase; enzyme inhibition, transferase
• Biological source: Hepatitis C virus subtype 1b
• Cellular location: Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein. Core protein p19: Virion . Envelope glycoprotein E1: Virion membrane ; Single-pass type I membrane protein . Envelope glycoprotein E2: Virion membrane ; Single-pass type I membrane protein . p7: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Protease NS2-3: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Serine protease NS3: Host endoplasmic reticulum membrane ; Peripheral membrane protein . Non-structural protein 4A: Host endoplasmic reticulum membrane ; Single-pass type I membrane protein . Non-structural protein 4B: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Non-structural protein 5A: Host endoplasmic reticulum membrane ; Peripheral membrane protein . RNA-directed RNA polymerase: Host endoplasmic reticulum membrane ; Single-pass type I membrane protein : P26663
• Total number of polymer chains: 2
• Total formula weight: 129624.13

Authors

Wang, M.,Ng, K.K.S.,Cherney, M.M.,Chan, L.,Yannopoulos, C.G.,Bedard, J.,Morin, N.,Nguyen-Ba, N.,Alaoui-Ismaili, M.H.,Bethell, R.C.,James, M.N.G. (deposition date: 2002-12-19, release date: 2003-03-18, Last modification date: 2024-11-06)

Primary citation

Wang, M.,Ng, K.K.S.,Cherney, M.M.,Chan, L.,Yannopoulos, C.G.,Bedard, J.,Morin, N.,Nguyen-Ba, N.,Alaoui-Ismaili, M.H.,Bethell, R.C.,James, M.N.G.
Non-Nucleoside Analogue Inhibitors Bind to an Allosteric Site on HCV NS5B Polymerase: Crystal Structures and Mechanism of Inhibition
J.Biol.Chem., 278:9489-9495, 2003

PubMed Abstract: X-ray crystal structures of two non-nucleoside analogue inhibitors bound to hepatitis C virus NS5B RNA-dependent RNA polymerase have been determined to 2.0 and 2.9 A resolution. These noncompetitive inhibitors bind to the same site on the protein, approximately 35 A from the active site. The common features of binding include a large hydrophobic region and two hydrogen bonds between both oxygen atoms of a carboxylate group on the inhibitor and two main chain amide nitrogen atoms of Ser(476) and Tyr(477) on NS5B. The inhibitor-binding site lies at the base of the thumb domain, near its interface with the C-terminal extension of NS5B. The location of this inhibitor-binding site suggests that the binding of these inhibitors interferes with a conformational change essential for the activity of the polymerase.

PubMed: 12509436
DOI: 10.1074/jbc.M209397200

Experimental method

X-RAY DIFFRACTION (2.9 Å)