biostudies-literatureBeran RKHoward Hughes Medical InstituteNIGMS NIH HHS29929-37https://www.ebi.ac.uk/biostudies/studies/S-EPMC2573085biostudies-literatureUnknown283(44)Non-structural protein 3 (NS3) is a multifunctional enzyme possessing serine protease, NTPase, and RNA unwinding activities that are required for hepatitis C viral (HCV) replication. HCV non-structural protein 4A (NS4A) binds to the N-terminal NS3 protease domain to stimulate NS3 serine protease activity. In addition, the NS3 protease domain enhances the RNA binding, ATPase, and RNA unwinding activities of the C-terminal NS3 helicase domain (NS3hel). To determine whether NS3hel enhances the NS3 serine protease activity, we purified truncated and full-length NS3-4A complexes and examined their serine protease activities under a variety of salt and pH conditions. Our results indicate that the helicase domain enhances serine protease activity, just as the protease domain enhances helicase actThe Journal of biological chemistryHepatitis C viral NS3-4A protease activity is enhanced by the NS3 helicase.PMC2573085GM60620F32 GM071120-01A1Pyle AMBeran RKfalseHepatitis C viral NS3-4A protease activity is enhanced by the NS3 helicase.Non-structural protein 3 (NS3) is a multifunctional enzyme possessing serine protease, NTPase, and RNA unwinding activities that are required for hepatitis C viral (HCV) replication. HCV non-structural protein 4A (NS4A) binds to the N-terminal NS3 protease domain to stimulate NS3 serine protease activity. In addition, the NS3 protease domain enhances the RNA binding, ATPase, and RNA unwinding activities of the C-terminal NS3 helicase domain (NS3hel). To determine whether NS3hel enhances the NS3 serine protease activity, we purified truncated and full-length NS3-4A complexes and examined their serine protease activities under a variety of salt and pH conditions. Our results indicate that the helicase domain enhances serine protease activity, just as the protease domain enhances helicase act2008-01-01T00:00:00Z2008 Oct2025-04-05T15:58:45.412Z2019-03-27T00:19:04ZS-EPMC25730851872351210.1074/jbc.M804065200