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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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.