The N-terminal region of NS3 serine proteinase of hepatitis C virus is important to maintain its enzymatic integrity.
Hepatitis C virus codes a serine proteinase in nonstructural protein 3 (NS3) to produce viral replicative machinery. Recently, we reported that the activity of NS3 proteinase (region 1050-1214) was efficiently inhibited by some chelators. Kinetic analysis revealed that its K(m) value was 3.9 mM. In contrast, an enzyme covering region 1027-1214 (including N-terminal region of NS3) was found to show an improved K(m) of 0.3 mM and a remarkably reduced susceptibility to EDTA. These results suggest that the N-terminal region of NS3 is not essential for the proteinase activity but indispensable to maintain its structural integrity.
Mori
A
A
Molecular Medicine, Laboratory, Yokohama Research Center, Mitsubishi Chemical Corp, Japan.
Yuasa
S
S
Yamada
K
K
Nagami
Y
Y
Miyamura
T
T
D000595:Amino Acid Sequence; D001665:Binding Sites; D002614:Chelating Agents / Q000494:pharmacology; D006526:Hepatitis C / Q000201:enzymology*; D007526:Isoelectric Point; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D002614:Chelating Agents; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases