Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.4.21.98 extracted from

  • Johnson, C.L.; Owen, D.M.; Gale, M.
    Functional and therapeutic analysis of hepatitis C virus NS3.4A protease control of antiviral immune defense (2007), J. Biol. Chem., 282, 10792-10803.
    View publication on PubMed
Search for more literature for 3.4.21.98

Application

Application Comment Organism
drug development NS3 protease domain and minimal NS4A cofactor are sufficient to inhibit antiviral signaling through retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5 and block activation of the downstream transcription factors interferon regulatory factor-3 and nuclear factor kappaB, accomplished by protease domain targeting and cleavage of interferon promoter stimulator-1. NS3-4A protease inhibitor therapy of hepatitis C virus infection can effectively remove the NS3-4A blockade to the innate immune response, restoring retinoic acid-inducible gene-I signaling to interferon promoter stimulator-1 and activation of IFN-stimulated gene expression in infected cells Hepacivirus C

Cloned(Commentary)

Cloned (Comment) Organism
NS3-4A wild-type and mutants expressed in Huh7 cells. HEK-293 cells transiently transfected with NS3 construct followed by Sendai virus infection Hepacivirus C

Protein Variants

Protein Variants Comment Organism
additional information NS3 mutants lacking the helicase domain retained the ability to control virus signaling initiated by retinoic acid-inducible gene-I or melanoma differentiation antigen 5 and suppress the downstream activation of interferon regulatory factor-3 and nuclear factor kappaB through the targeted proteolysis of interferon promoter stimulator-1. Regulation is abrogated by truncation of the NS3 protease domain or by point mutations that ablate protease activity Hepacivirus C
S1165A full-length NS3-4A harboring a protease activate site mutation, cannot cleave NS5AB polyprotein Hepacivirus C

Inhibitors

Inhibitors Comment Organism Structure
ITMN-C active site inhibitor of the NS3-4A protease Hepacivirus C
SCH6 active site inhibitor of the NS3-4A protease Hepacivirus C

Organism

Organism UniProt Comment Textmining
Hepacivirus C
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
interferon promoter stimulator-1 + H2O protease domain of NS3-4A is sufficient for targeting and cleavage. Targeted cleavage inhibits downstream signaling to interferon regulatory factor-3 and nuclear factor kappaB Hepacivirus C ?
-
 ?
NS5AB polyprotein + H2O
-
 Hepacivirus C ?
-
 ?

Synonyms

Synonyms Comment Organism
NS3-4A
-
 Hepacivirus C
NS3-4A protease
-
 Hepacivirus C

Cofactor

Cofactor Comment Organism Structure
additional information efficient NS3-4A proteolytic activity requires the protease domain and its NS4A cofactor but does not require the NS3 helicase domain Hepacivirus C