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PDBsum entry 4b6e
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References listed in PDB file
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Key reference
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Title
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Discovery of an allosteric mechanism for the regulation of hcv ns3 protein function.
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Authors
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S.M.Saalau-Bethell,
A.J.Woodhead,
G.Chessari,
M.G.Carr,
J.Coyle,
B.Graham,
S.D.Hiscock,
C.W.Murray,
P.Pathuri,
S.J.Rich,
C.J.Richardson,
P.A.Williams,
H.Jhoti.
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Ref.
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Nat Chem Biol, 2012,
8,
920-925.
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PubMed id
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Abstract
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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.
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