Format

Send to

Choose Destination
Nat Chem Biol. 2012 Nov;8(11):920-5. doi: 10.1038/nchembio.1081. Epub 2012 Sep 30.

Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function.

Author information

1
Astex Pharmaceuticals, Cambridge Science Park, Cambridge, UK.

Abstract

Here we report a highly conserved new binding site located at the interface between the protease and helicase domains of the hepatitis C virus (HCV) NS3 protein. Using a chemical lead, identified by fragment screening and structure-guided design, we demonstrate that this site has a regulatory function on the protease activity via an allosteric mechanism. We propose that compounds binding at this allosteric site inhibit the function of the NS3 protein by stabilizing an inactive conformation and thus represent a new class of direct-acting antiviral agents.

PMID:
23023261
PMCID:
PMC3480716
DOI:
10.1038/nchembio.1081
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center