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NS3 Protease from Hepatitis C Virus: Biophysical Studies on an Intrinsically Disordered Protein Domain
Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Unit BIFI-IQFR (CSIC), University of Zaragoza, Zaragoza 50018, Spain
Institute of Molecular and Cell Biology, Miguel Hernandez University, Elche (Alicante) 03202, Spain
Advanced Microscopy Laboratory (LMA), Institute of Nanoscience of Aragon (INA), University of Zaragoza, Zaragoza 50018, Spain
ARAID Foundation, Government of Aragon, Zaragoza 50018, Spain
IIS Aragon–Aragon Health Science Institute (I+CS), Zaragoza 50009, Spain
Network Biomedical Research Center on Hepatic and Digestive Diseases (CIBERehd), Barcelona 08036, Spain
Department of Biochemistry and Cellular and Molecular Biology, Faculty of Sciences, University of Zaragoza, Zaragoza 50009, Spain
* Authors to whom correspondence should be addressed.
Received: 22 April 2013; in revised form: 4 June 2013 / Accepted: 13 June 2013 / Published: 26 June 2013
Abstract: The nonstructural protein 3 (NS3) from the hepatitis C virus (HCV) is responsible for processing the non-structural region of the viral precursor polyprotein in infected hepatic cells. NS3 protease activity, located at the N-terminal domain, is a zinc-dependent serine protease. A zinc ion, required for the hydrolytic activity, has been considered as a structural metal ion essential for the structural integrity of the protein. In addition, NS3 interacts with another cofactor, NS4A, an accessory viral protein that induces a conformational change enhancing the hydrolytic activity. Biophysical studies on the isolated protease domain, whose behavior is similar to that of the full-length protein (e.g., catalytic activity, allosteric mechanism and susceptibility to inhibitors), suggest that a considerable global conformational change in the protein is coupled to zinc binding. Zinc binding to NS3 protease can be considered as a folding event, an extreme case of induced-fit binding. Therefore, NS3 protease is an intrinsically (partially) disordered protein with a complex conformational landscape due to its inherent plasticity and to the interaction with its different effectors. Here we summarize the results from a detailed biophysical characterization of this enzyme and present new experimental data.
Keywords: NS3 protease; protein folding and stability; ligand binding; conformational landscape; intrinsically disordered protein
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MDPI and ACS Style
Vega, S.; Neira, J.L.; Marcuello, C.; Lostao, A.; Abian, O.; Velazquez-Campoy, A. NS3 Protease from Hepatitis C Virus: Biophysical Studies on an Intrinsically Disordered Protein Domain. Int. J. Mol. Sci. 2013, 14, 13282-13306.
Vega S, Neira JL, Marcuello C, Lostao A, Abian O, Velazquez-Campoy A. NS3 Protease from Hepatitis C Virus: Biophysical Studies on an Intrinsically Disordered Protein Domain. International Journal of Molecular Sciences. 2013; 14(7):13282-13306.
Vega, Sonia; Neira, Jose L.; Marcuello, Carlos; Lostao, Anabel; Abian, Olga; Velazquez-Campoy, Adrian. 2013. "NS3 Protease from Hepatitis C Virus: Biophysical Studies on an Intrinsically Disordered Protein Domain." Int. J. Mol. Sci. 14, no. 7: 13282-13306.