Cloned (Comment) | Organism |
---|---|
wild-type or mutants V36M, V36L, A156T expressed in Escherichia coli BL21(DE3) | Hepacivirus C |
Crystallization (Comment) | Organism |
---|---|
mutant V36M in a complex with NS4A cofactor peptide, at 2.4 A resolution | Hepacivirus C |
Protein Variants | Comment | Organism |
---|---|---|
A156T | replicon capacity 16% as compared to wild-type | Hepacivirus C |
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 |
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 |
V36A/A156T | more than 62fold loss of sensitivity to telaprevir. Replicon capacity 9% as compared to wild-type | Hepacivirus C |
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 |
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 |
V36A/T54A | 20.1fold loss of sensitivity to telaprevir. Replicon capacity 8% as compared to wild-type | Hepacivirus C |
V36G | 11.2fold loss of sensitivity to telaprevir. Replicon capacity 59% as compared to wild-type | Hepacivirus C |
V36L | 2.2fold loss of sensitivity to telaprevir | Hepacivirus C |
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 |
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 |
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 | Comment | Organism | Structure |
---|---|---|---|
IFN-alpha | - |
Hepacivirus C | |
ribavirin | - |
Hepacivirus C | |
telaprevir | - |
Hepacivirus C |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.029 | - |
EDVV-4-aminobutyryl-CSMSY | mutant V36L, in the presence of cofactor peptide KKGSVVIVGRIVLSCK | Hepacivirus C | |
0.051 | - |
EDVV-4-aminobutyryl-CSMSY | mutant V36M, in the presence of cofactor peptide KKGSVVIVGRIVLSCK | Hepacivirus C | |
0.053 | - |
EDVV-4-aminobutyryl-CSMSY | wild-type, genotype 1a, in the presence of cofactor peptide KKGSVVIVGRIVLSCK | Hepacivirus C | |
0.18 | - |
EDVV-4-aminobutyryl-CSMSY | mutant V36M/R155K, in the presence of cofactor peptide KKGSVVIVGRIVLSCK | Hepacivirus C | |
0.29 | - |
EDVV-4-aminobutyryl-CSMSY | wild-type, genotype 1b, in the presence of cofactor peptide KKGSVVIVGRIVLSCK | Hepacivirus C | |
0.38 | - |
EDVV-4-aminobutyryl-CSMSY | mutant V36A, in the presence of cofactor peptide KKGSVVIVGRIVLSCK | Hepacivirus C |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Hepacivirus C | - |
- |
- |
Hepacivirus C H | - |
- |
- |
Purification (Comment) | Organism |
---|---|
mutant V36M purified by Ni-resin and gel filtraton | Hepacivirus C |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
acetyl-DED(EDANS)EEalpha-aminobutyryl-psi(COO)ASK(DABCYL)-NH2 + H2O | - |
Hepacivirus C | ? | - |
? | |
acetyl-DED(EDANS)EEalpha-aminobutyryl-psi(COO)ASK(DABCYL)-NH2 + H2O | - |
Hepacivirus C H | ? | - |
? | |
EDVV-4-aminobutyryl-CSMSY + H2O | - |
Hepacivirus C | EDVV-4-aminobutyryl-C + SMSY | - |
? | |
EDVV-4-aminobutyryl-CSMSY + H2O | - |
Hepacivirus C H | EDVV-4-aminobutyryl-C + SMSY | - |
? |
Subunits | Comment | Organism |
---|---|---|
homodimer | crystallography, one NS3 protease domain molecule and one molecule of the NS4A cofactor | Hepacivirus C |
Synonyms | Comment | Organism |
---|---|---|
NS3-4A serine protease | - |
Hepacivirus C |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
KKGSVVIVGRIVLSCK | - |
Hepacivirus C | |
additional information | NS4A cofactor peptide | Hepacivirus C |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.00005 | - |
wild-type, genotype 1a | Hepacivirus C | telaprevir | |
0.000063 | - |
wild-type, genotype 1b | Hepacivirus C | telaprevir | |
0.00013 | - |
mutant V36L | Hepacivirus C | telaprevir | |
0.00023 | - |
mutant V36A | Hepacivirus C | telaprevir | |
0.00027 | - |
mutant V36M | Hepacivirus C | telaprevir | |
0.0034 | - |
mutant V36M/R155K | Hepacivirus C | telaprevir |