Helicase, a target for novel inhibitors of hepatitis C virus.
Virus-encoded enzymes of hepatitis C virus (HCV) were identified from its genome sequence. This allows application of drug discovery strategies which rely on inhibition of enzymes unique to HCV. Discovery of high-affinity inhibitors is facilitated by knowledge of the target enzyme's three-dimensional structure. For development of inhibitors of the HCV helicase, which belongs to a class of enzymes for which little structural information is available, the impact of structural information on the drug discovery process is greater than for targets belonging to well-characterized classes of enzyme. Here the structure of the HCV helicase is described. Regions required for enzymatic activity, which are also the preferred sites of drug interaction, are highlighted.
Yao
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Schering-Plough Research Institute, Kenilworth, New Jersey, USA.
Weber
P C
PC
D017766:Acid Anhydride Hydrolases / Q000737:chemistry; D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors; D016174:Hepacivirus / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D043583:Nucleoside-Triphosphatase; D017510:Protein Folding; D017433:Protein Structure, Secondary; D020365:RNA Helicases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000378:metabolism*; D012697:Serine Endopeptidases; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D017766:Acid Anhydride Hydrolases; D004791:Enzyme Inhibitors; D043583:Nucleoside-Triphosphatase; D020365:RNA Helicases; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases