Recent advances in the analysis of HCV NS5B RNA-dependent RNA polymerase.
An RNA-dependent RNA polymerase denoted nonstructural protein 5B (NS5B) is the central enzyme in replication of the hepatitis C virus genome. Recent advances in the biochemical and structural understanding of NS5B include solubilization and purification of the full-length enzyme and various truncated forms. In vitro conditions for NS5B-catalyzed primer elongation using both homo- and heteropolymeric RNA templates were discovered. The crystal structure of the NS5B apoenzyme revealed a globular shape unique among polymerases, and implicated new structural features important for binding the RNA template and cognate ribonucleotide substrates. The crystallographic results also provided a structure-based framework for biochemical analyses and drug-design efforts. Finally, inhibitors of HCV RNA-dependent RNA polymerase have been reported.
Department of Structural Chemistry, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. Charles.Lesburg@spcorp.com
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D000595:Amino Acid Sequence; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016174:Hepacivirus / Q000201:enzymology*; D006801:Humans; D008969:Molecular Sequence Data; D012324:RNA-Dependent RNA Polymerase / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
D004791:Enzyme Inhibitors; D012324:RNA-Dependent RNA Polymerase