Abstract
In flaviviruses and hepatitis C virus (HCV), the NS3 gene encodes the N-terminal protease (NS3pro) and the C-terminal helicase (NS3hel). In HCV, the downstream NS4A is required for the NS3pro activity and exhibits a conserved EFDEMEE motif. To identify the role of this motif, we compared the ATPase and helicase activities of NS3 alone with those of the NS3-NS4A constructs. Our results suggest that the EFDEMEE motif is essential for regulating the ATPase activity of NS3hel. It is likely that this motif interferes with the ATP-binding site of NS3hel. It is becoming clear that NS4A functions as a cofactor of both proteinase and helicase in HCV.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adenosine Triphosphatases / chemistry
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Adenosine Triphosphatases / genetics
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Adenosine Triphosphatases / metabolism
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Adenosine Triphosphate / metabolism
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Amino Acid Motifs
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Amino Acid Sequence
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Amino Acid Substitution
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Base Sequence
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Binding Sites / genetics
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Carrier Proteins / chemistry
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism*
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DNA Primers / genetics
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Genes, Viral
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Hepacivirus / genetics*
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Hepacivirus / metabolism*
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Humans
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Hydrolysis
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Intracellular Signaling Peptides and Proteins
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Models, Molecular
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Protein Conformation
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RNA Helicases / chemistry
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RNA Helicases / genetics
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RNA Helicases / metabolism
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Sequence Homology, Amino Acid
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Viral Nonstructural Proteins / chemistry
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Viral Nonstructural Proteins / genetics*
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Viral Nonstructural Proteins / metabolism*
Substances
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Carrier Proteins
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DNA Primers
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Intracellular Signaling Peptides and Proteins
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NS3 protein, hepatitis C virus
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NS4A cofactor peptide, Hepatitis C virus
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Recombinant Fusion Proteins
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Viral Nonstructural Proteins
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Adenosine Triphosphate
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Adenosine Triphosphatases
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RNA Helicases