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Literature summary extracted from

  • Zhou, Y.; Bartels, D.J.; Hanzelka, B.L.; Mueh, U.; Wei, Y.; Chu, H.M.; Tigges, A.M.; Brennan, D.L.; Rao, B.G.; Swenson, L.; Kwong, A.D.; Lin, C.
    Phenotypic characterization of resistant Val36 variants of hepatitis C virus NS3-4A serine protease (2008), Antimicrob. Agents Chemother., 52, 110-120.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
3.4.21.98 wild-type or mutants V36M, V36L, A156T expressed in Escherichia coli BL21(DE3) Hepacivirus C

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
3.4.21.98 mutant V36M in a complex with NS4A cofactor peptide, at 2.4 A resolution Hepacivirus C

Protein Variants

EC Number Protein Variants Comment Organism
3.4.21.98 A156T replicon capacity 16% as compared to wild-type Hepacivirus C
3.4.21.98 T54A 6.3fold loss of sensitivity to telaprevir. Replicon capacity 65% as compared to wild-type. Remains fully sensitive to IFN-alpha and ribavirin Hepacivirus C
3.4.21.98 V34A 7.4fold loss of sensitivity to telaprevir. Replicon capacity 104% as compared to wild-type. Remains fully sensitive to IFN-alpha and ribavirin Hepacivirus C
3.4.21.98 V36A/A156T more than 62fold loss of sensitivity to telaprevir. Replicon capacity 9% as compared to wild-type Hepacivirus C
3.4.21.98 V36A/R155K ca. 40fold loss of sensitivity to telaprevir. Replicon capacity 57% as compared to wild-type. Remains fully sensitive to IFN-alpha and ribavirin Hepacivirus C
3.4.21.98 V36A/R155T more than 62fold loss of sensitivity to telaprevir. Replicon capacity 23% as compared to wild-type. Remains fully sensitive to IFN-alpha and ribavirin Hepacivirus C
3.4.21.98 V36A/T54A 20.1fold loss of sensitivity to telaprevir. Replicon capacity 8% as compared to wild-type Hepacivirus C
3.4.21.98 V36G 11.2fold loss of sensitivity to telaprevir. Replicon capacity 59% as compared to wild-type Hepacivirus C
3.4.21.98 V36L 2.2fold loss of sensitivity to telaprevir Hepacivirus C
3.4.21.98 V36M except for the side chain of Met36, the V36M variant structure is identical to that of the wild-type apoenzyme. 7fold loss of sensitivity to telaprevir. Replicon capacity 77% as compared to wild-type. Remains fully sensitive to IFN-alpha and ribavirin Hepacivirus C
3.4.21.98 V36M/R155K ca. 62fold loss of sensitivity to telaprevir. Replicon capacity 42% as compared to wild-type. Remains fully sensitive to IFN-alpha and ribavirin Hepacivirus C
3.4.21.98 V36M/R155T more than 62fold loss of sensitivity to telaprevir. Replicon capacity 36% as compared to wild-type. Remains fully sensitive to IFN-alpha and ribavirin Hepacivirus C

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.4.21.98 IFN-alpha
-
 Hepacivirus C
3.4.21.98 ribavirin
-
 Hepacivirus C
3.4.21.98 telaprevir
-
 Hepacivirus C

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
3.4.21.98 0.029
-
 EDVV-4-aminobutyryl-CSMSY mutant V36L, in the presence of cofactor peptide KKGSVVIVGRIVLSCK Hepacivirus C
3.4.21.98 0.051
-
 EDVV-4-aminobutyryl-CSMSY mutant V36M, in the presence of cofactor peptide KKGSVVIVGRIVLSCK Hepacivirus C
3.4.21.98 0.053
-
 EDVV-4-aminobutyryl-CSMSY wild-type, genotype 1a, in the presence of cofactor peptide KKGSVVIVGRIVLSCK Hepacivirus C
3.4.21.98 0.18
-
 EDVV-4-aminobutyryl-CSMSY mutant V36M/R155K, in the presence of cofactor peptide KKGSVVIVGRIVLSCK Hepacivirus C
3.4.21.98 0.29
-
 EDVV-4-aminobutyryl-CSMSY wild-type, genotype 1b, in the presence of cofactor peptide KKGSVVIVGRIVLSCK Hepacivirus C
3.4.21.98 0.38
-
 EDVV-4-aminobutyryl-CSMSY mutant V36A, in the presence of cofactor peptide KKGSVVIVGRIVLSCK Hepacivirus C

Organism

EC Number Organism UniProt Comment Textmining
3.4.21.98 Hepacivirus C
-
-
-
3.4.21.98 Hepacivirus C H
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
3.4.21.98 mutant V36M purified by Ni-resin and gel filtraton Hepacivirus C

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.4.21.98 acetyl-DED(EDANS)EEalpha-aminobutyryl-psi(COO)ASK(DABCYL)-NH2 + H2O
-
 Hepacivirus C ?
-
 ?
3.4.21.98 acetyl-DED(EDANS)EEalpha-aminobutyryl-psi(COO)ASK(DABCYL)-NH2 + H2O
-
 Hepacivirus C H ?
-
 ?
3.4.21.98 EDVV-4-aminobutyryl-CSMSY + H2O
-
 Hepacivirus C EDVV-4-aminobutyryl-C + SMSY
-
 ?
3.4.21.98 EDVV-4-aminobutyryl-CSMSY + H2O
-
 Hepacivirus C H EDVV-4-aminobutyryl-C + SMSY
-
 ?

Subunits

EC Number Subunits Comment Organism
3.4.21.98 homodimer crystallography, one NS3 protease domain molecule and one molecule of the NS4A cofactor Hepacivirus C

Synonyms

EC Number Synonyms Comment Organism
3.4.21.98 NS3-4A serine protease
-
 Hepacivirus C

Cofactor

EC Number Cofactor Comment Organism Structure
3.4.21.98 KKGSVVIVGRIVLSCK
-
 Hepacivirus C
3.4.21.98 additional information NS4A cofactor peptide Hepacivirus C

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
3.4.21.98 0.00005
-
 wild-type, genotype 1a Hepacivirus C telaprevir
3.4.21.98 0.000063
-
 wild-type, genotype 1b Hepacivirus C telaprevir
3.4.21.98 0.00013
-
 mutant V36L Hepacivirus C telaprevir
3.4.21.98 0.00023
-
 mutant V36A Hepacivirus C telaprevir
3.4.21.98 0.00027
-
 mutant V36M Hepacivirus C telaprevir
3.4.21.98 0.0034
-
 mutant V36M/R155K Hepacivirus C telaprevir