2AX0

Hepatitis C Virus NS5b RNA Polymerase in complex with a covalent inhibitor (5x)

Summary for 2AX0

• Entry DOI: 10.2210/pdb2ax0/pdb
• Descriptor: Genome polyprotein, SULFATE ION, 5R-(2E-METHYL-3-PHENYL-ALLYL)-3-(BENZENESULFONYLAMINO)-4-OXO-2-THIONOTHIAZOLIDINE, ... (4 entities in total)
• Functional Keywords: hcv, ns5b, polymerase, fingers, thumb, palm, transferase
• Biological source: Hepatitis C virus
• Cellular location: Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein. Core protein p19: Virion (By similarity). Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein (Potential). Envelope glycoprotein E2: Virion membrane; Single-pass type I membrane protein (Potential). p7: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Protease NS2-3: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). Non-structural protein 4A: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). RNA-directed RNA polymerase: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential): P26663
• Total number of polymer chains: 2
• Total formula weight: 130785.68

Authors

Powers, J.P.,Piper, D.E.,Li, Y.,Mayorga, V.,Anzola, J.,Chen, J.M.,Jaen, J.C.,Lee, G.,Liu, J.,Peterson, M.G.,Tonn, G.R.,Ye, Q.,Walker, N.P.,Wang, Z. (deposition date: 2005-09-02, release date: 2006-01-24, Last modification date: 2024-10-16)

Primary citation

Powers, J.P.,Piper, D.E.,Li, Y.,Mayorga, V.,Anzola, J.,Chen, J.M.,Jaen, J.C.,Lee, G.,Liu, J.,Peterson, M.G.,Tonn, G.R.,Ye, Q.,Walker, N.P.,Wang, Z.
SAR and Mode of Action of Novel Non-Nucleoside Inhibitors of Hepatitis C NS5b RNA Polymerase.
J.Med.Chem., 49:1034-1046, 2006

PubMed Abstract: Novel non-nucleoside inhibitors of the HCV RNA polymerase (NS5b) with sub-micromolar biochemical potency have been identified which are selective for the inhibition of HCV NS5b over other polymerases. The structures of the complexes formed between several of these inhibitors and HCV NS5b were determined by X-ray crystallography, and the inhibitors were found to bind in an allosteric binding site separate from the active site. Structure-activity relationships and structural studies have identified the mechanism of action for compounds in this series, several of which possess drug-like properties, as unique, reversible, covalent inhibitors of HCV NS5b.

PubMed: 16451069
DOI: 10.1021/jm050859x

Experimental method

X-RAY DIFFRACTION (2 Å)