[HTML][HTML] Interdomain communication in hepatitis C virus polymerase abolished by small molecule inhibitors bound to a novel allosteric site
S Di Marco, C Volpari, L Tomei, S Altamura… - Journal of Biological …, 2005 - ASBMB
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-Å 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 pockets, whereas a carboxylate substituent forms a salt …
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-Å 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 pockets, whereas a carboxylate substituent forms a salt …