Identification of the protease domain in NS3 of hepatitis C virus.
NS3 of hepatitis C virus (HCV) is a serine protease that carries out the proteolytic processing of the nonstructural proteins of the HCV polyprotein. Deletion analysis of the N terminus of NS2,3,4 fusion protein revealed that the N-terminal boundary of the active protease resides between amino acids 1050 and 1083. The processing patterns of internal deletion mutants of NS2,3,4 indicated that the C terminus of the enzymically active protease resides between amino acids 1115 and 1218. The N- and C-terminal boundaries of the protease were also confirmed by determining the trans-cleavage activity of internally deleted NS3,4. NS3 protease activity was inhibited by Cu2+ but was slightly enhanced by Zn2+. This report provides a possible approach for development of antiviral agents based on protease inhibitors.
Han
D S
DS
Department of Life Science, Pohang University of Science and Technology, Kyungbuk, Korea.
Hahm
B
B
Rho
H M
HM
Jang
S K
SK
D001665:Binding Sites; D003300:Copper; D016174:Hepacivirus / Q000201:enzymology*; D006801:Humans; D016296:Mutagenesis; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015032:Zinc; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D003300:Copper; D011993:Recombinant Fusion Proteins; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; D015032:Zinc; C097010:NS2 protein, Hepatitis C virus; C084422:NS3 protein, hepatitis C virus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus