6533b862fe1ef96bd12c6d32
RESEARCH PRODUCT
The NS3/4A proteinase of the hepatitis C virus: unravelling structure and function of an unusual enzyme and a prime target for antiviral therapy
Ralf Bartenschlagersubject
Models MolecularProtein ConformationvirusesHepatitis C virusMolecular Sequence DataHepacivirusViral Nonstructural ProteinsBiologymedicine.disease_causeAntiviral AgentsSerineProtein structureVirologymedicineProtease InhibitorsAmino Acid SequenceHepatitischemistry.chemical_classificationNS3HepatologySerine EndopeptidasesRNAmedicine.diseaseVirologyNS2-3 proteaseInfectious DiseasesEnzymechemistryRNA Helicasesdescription
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.
year | journal | country | edition | language |
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1999-12-22 | Journal of Viral Hepatitis |