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Literature summary for 3.6.4.13 extracted from

  • Frick, D.N.
    The hepatitis C virus NS3 protein: a model RNA helicase and potential drug target (2007), Curr. Issues Mol. Biol., 9, 1-20.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.6.4.13

Crystallization (Commentary)

Crystallization (Comment) Organism
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 Hepacivirus C

Protein Variants

Protein Variants Comment Organism
H293A mutation results in a protein with a significantly higher level of ATPase in the absence of RNA. The mutant protein still unwinds RNA. In the presence of RNA, the H293A mutant hydrolyzes ATP slower than wild-type Hepacivirus C

Inhibitors

Inhibitors Comment Organism Structure
dATP inhibits unwinding Hepacivirus C
tetrabromobenzotriazole inhibits unwinding, no inhibition of ATP hydrolysis Hepacivirus C

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + H2O Hepacivirus C the C-terminal portion of hepatitis C virus nonstructural protein 3 (NS3) forms a three domain polypeptide that possesses the ability to travel along RNA or single-stranded DNA (ssDNA) in a 3’ to 5’ direction. Driven by the energy of ATP hydrolysis, this movement allows the protein to displace complementary strands of DNA or RNA ADP + phosphate
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Organism

Organism UniProt Comment Textmining
Hepacivirus C
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Purification (Commentary)

Purification (Comment) Organism
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 Hepacivirus C

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + H2O the C-terminal portion of hepatitis C virus nonstructural protein 3 (NS3) forms a three domain polypeptide that possesses the ability to travel along RNA or single-stranded DNA (ssDNA) in a 3’ to 5’ direction. Driven by the energy of ATP hydrolysis, this movement allows the protein to displace complementary strands of DNA or RNA Hepacivirus C ADP + phosphate
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ATP + H2O the protein binds RNA and DNA in a sequence specific manner. ATP hydrolysis is stimulated by some nucleic acid polymers much better than it is stimulated by others. The range is quite dramatic. Poly(G) RNA does not stimulate at any measurable level, and poly(U) RNA (or DNA) stimulates best (up to 50 fold). HCV helicase unwinds a DNA duplex more efficiently than an RNA duplex. ATP binds HCV helicase between two RecA-like domains, causing a conformational change that leads to a decrease in the affinity of the protein for nucleic acids. One strand of RNA binds in a second cleft formed perpendicular to the ATP-binding cleft and its binding leads to stimulation of ATP hydrolysis. RNA and/or ATP binding likely causes rotation of domain 2 of the enzyme relative to domains 1 and 3, and somehow this conformational change allows the protein to move like a motor Hepacivirus C ADP + phosphate
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additional information the mature NS3 protein comprises 5 domains: the N-terminal 2 domains form the serine protease along with the NS4A cofactor, and the C-terminal 3 domains form the helicase. The helicase portion of NS3 can be separated form the protease portion by cleaving a linker. Since the protease portion is more hydrophobic, removing it allows the NS3 helicase fragment to be expressed as a more soluble protein at higher levels in Escherichia coli. The fragment of NS3 possessing helicase activity is referred to as HCV helicase Hepacivirus C ?
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IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.06
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 Hepacivirus C tetrabromobenzotriazole