title: The NS3/4A proteinase of the hepatitis C virus: unravelling structure and function of an unusual enzyme and a prime target for antiviral therapy.
abstract: The hepatitis C virus (HCV) is a major causative agent of transfusion-acquired and sporadic non-A, non-B hepatitis worldwide. Infections most often persist and lead, in approximately 50% of all patients, to chronic liver disease. As is characteristic for a member of the family Flaviviridae, HCV has a plus-strand RNA genome encoding a polyprotein, which is cleaved co- and post-translationally into at least 10 different products. These cleavages are mediated, among others, by a virally encoded chymotrypsin-like serine proteinase located in the N-terminal domain of non-structural protein 3 (NS3). Activity of this enzyme requires NS4A, a 54-residue polyprotein cleavage product, to form a stable complex with the NS3 domain. This review will describe the biochemical properties of the NS3/4A proteinase, its X-ray crystal structure and current attempts towards development of efficient inhibitors.
authors.affiliation: Institute for Virology, Johannes-Gutenberg University Mainz, Mainz, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Bartenschlager
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000494:pharmacology; D011487:Protein Conformation; D020365:RNA Helicases; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D011480:Protease Inhibitors; D020365:RNA Helicases; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases