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Literature summary extracted from
- Phenotypic and structural analyses of hepatitis C virus NS3 protease Arg155 variants: sensitivity to telaprevir (VX-950) and interferon alpha (2007), J. Biol. Chem., 282, 22619-22628.
Application
| EC Number | Application | Comment | Organism |
|---|---|---|---|
| 3.4.21.98 | drug development | combination with IFN-alpha with or without ribavirin may be a potential therapeutic strategy to suppress the emergence of Hepatitis C virus variants with substitutions at NS3 protease residue 155 | Hepacivirus C |
Cloned(Commentary)
| EC Number | Cloned (Comment) | Organism |
|---|---|---|
| 3.4.21.98 | wild-type or mutants R155K, R155T, R155S, and R155I expressed from the corresponding pBEV10/HCV-3201/NS3181-His6 plasmids in BL21/DE3 Escherichia coli cells. Mutant R155K, fused to a T7 tag at the N terminus and a His6 tag at the C terminus, expressed from pBEV10/HCV-H/NS3181-His6 containing the R155K variation in Escherichia coli BL21 (DE3) cells | Hepacivirus C |
Crystallization (Commentary)
| EC Number | Crystallization (Comment) | Organism |
|---|---|---|
| 3.4.21.98 | genotype 1a HCV protease domain with R155K mutation, in a complex with an NS4A co-factor peptide, at 2.5 A resolution. Crystals belong to space group R32 with unit cell dimensions of a=225.31 A, b=225.31 A, c=75.66 A, alpha=90°, beta=90°, and gamma=120° | Hepacivirus C |
Protein Variants
| EC Number | Protein Variants | Comment | Organism |
|---|---|---|---|
| 3.4.21.98 | R155G | decreased sensitivity to telaprevir and replication capacity in replicon cells | Hepacivirus C |
| 3.4.21.98 | R155I | decreased sensitivity to telaprevir and replication capacity in replicon cells | Hepacivirus C |
| 3.4.21.98 | R155K | crystal structure of the R155K protease is essentially identical to that of the wild-type apoenzyme except for the side chain of mutated residue 155. Decreased sensitivity to telaprevir and replication capacity in replicon cells. Remains fully sensitive to IFN-alpha | Hepacivirus C |
| 3.4.21.98 | R155M | decreased sensitivity to telaprevir and replication capacity in replicon cells. Remains fully sensitive to IFN-alpha | Hepacivirus C |
| 3.4.21.98 | R155S | decreased sensitivity to telaprevir and replication capacity in replicon cells | Hepacivirus C |
| 3.4.21.98 | R155T | decreased sensitivity to telaprevir and replication capacity in replicon cells. Remains fully sensitive to IFN-alpha | 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 | VX-950 | telaprevir | Hepacivirus C | |
KM Value [mM]
| EC Number | KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|---|
| 3.4.21.98 | 0.053 | - |
EDVV-Abu-CSMSY | wild-type | Hepacivirus C | |
| 3.4.21.98 | 0.068 | - |
EDVV-Abu-CSMSY | mutant R155T | Hepacivirus C | |
| 3.4.21.98 | 0.168 | - |
EDVV-Abu-CSMSY | mutant R155K | Hepacivirus C | |
| 3.4.21.98 | 0.552 | - |
EDVV-Abu-CSMSY | mutant R155S | Hepacivirus C | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 3.4.21.98 | Hepacivirus C | - |
- |
- |
Purification (Commentary)
| EC Number | Purification (Comment) | Organism |
|---|---|---|
| 3.4.21.98 | wild-type or mutants R155K, R155T, R155S, and R155I purified on affinity resin and by gel filtration. Purity over 90% (wild type and R155K) or around 80% (R155T and R155S) | Hepacivirus C |
Storage Stability
| EC Number | Storage Stability | Organism |
|---|---|---|
| 3.4.21.98 | -80°C | Hepacivirus C |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 3.4.21.98 | EDVV-Abu-CSMSY + H2O | - |
Hepacivirus C | ? | - |
? | |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 3.4.21.98 | NS3 protease | - |
Hepacivirus C |
| 3.4.21.98 | NS3-4A serine protease | - |
Hepacivirus C |
Cofactor
| EC Number | Cofactor | Comment | Organism | Structure |
|---|---|---|---|---|
| 3.4.21.98 | KKGSVVIVGRIVLSGK | cofactor peptide KK4A | Hepacivirus C | |
| 3.4.21.98 | KKGSVVIVGRIVLSGKPAIIPKK | NS-4A cofactor | Hepacivirus C | |
IC50 Value
| EC Number | IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|---|
| 3.4.21.98 | 0.00005 | - |
wild-type | Hepacivirus C | VX-950 | |
| 3.4.21.98 | 0.00049 | - |
mutant R155T | Hepacivirus C | VX-950 | |
| 3.4.21.98 | 0.00051 | - |
mutant R155K | Hepacivirus C | VX-950 | |
| 3.4.21.98 | 0.00088 | - |
mutant R155I | Hepacivirus C | VX-950 | |
| 3.4.21.98 | 0.00115 | - |
mutant R155S | Hepacivirus C | VX-950 | |
| 3.4.21.98 | 0.032 | - |
mutant R155T | Hepacivirus C | ribavirin | |
| 3.4.21.98 | 0.037 | - |
mutant R155K | Hepacivirus C | ribavirin | |
| 3.4.21.98 | 0.039 | - |
mutant R155M | Hepacivirus C | ribavirin | |
| 3.4.21.98 | 0.058 | - |
wild-type | Hepacivirus C | ribavirin | |
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