Interdomain communication in hepatitis C virus polymerase abolished by small molecule inhibitors bound to a novel allosteric site.

@article{Marco2005InterdomainCI,
  title={Interdomain communication in hepatitis C virus polymerase abolished by small molecule inhibitors bound to a novel allosteric site.},
  author={Stefania Di Marco and Cinzia Volpari and Licia Tomei and Sergio Altamura and Steven R. Harper and Frank Narjes and Uwe Koch and Michael Rowley and Raffaele De Francesco and Giovanni Migliaccio and Andrea Carf{\'i}},
  journal={The Journal of biological chemistry},
  year={2005},
  volume={280 33},
  pages={29765-70}
}
The hepatitis C virus (HCV) polymerase is required for replication of the viral genome and is a key target for therapeutic intervention against HCV. We have determined the crystal structures of the HCV polymerase complexed with two indole-based allosteric inhibitors at 2.3- and 2.4-Angstroms resolution. The structures show that these inhibitors bind to a site on the surface of the thumb domain. A cyclohexyl and phenyl ring substituents, bridged by an indole moiety, fill two closely spaced… CONTINUE READING