Structural and Regulatory Elements of HCV NS5B Polymerase – β-Loop and C-Terminal Tail – Are Required for Activity of Allosteric Thumb Site II Inhibitors

@inproceedings{Boyce2014StructuralAR,
  title={Structural and Regulatory Elements of HCV NS5B Polymerase – β-Loop and C-Terminal Tail – Are Required for Activity of Allosteric Thumb Site II Inhibitors},
  author={Sarah E. Boyce and Neeraj Tirunagari and Anita Niedziela-Majka and Jason Perry and Melanie R.-M. Wong and Elaine Kan and Leanna L Lagpacan and Ona Barauskas and Magdeleine Hung and Martijn Fenaux and Todd Appleby and William J. Watkins and Uli Schmitz and Roman Sakowicz},
  booktitle={PloS one},
  year={2014}
}
Elucidation of the mechanism of action of the HCV NS5B polymerase thumb site II inhibitors has presented a challenge. Current opinion holds that these allosteric inhibitors stabilize the closed, inactive enzyme conformation, but how this inhibition is accomplished mechanistically is not well understood. Here, using a panel of NS5B proteins with mutations in key regulatory motifs of NS5B--the C-terminal tail and β-loop--in conjunction with a diverse set of NS5B allosteric inhibitors, we show… CONTINUE READING