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Literature summary for 3.4.21.98 extracted from
- Characterisation of the role of zinc in the hepatitis C virus NS2/3 auto-cleavage and NS3 protease activities (2007), J. Mol. Biol., 366, 1652-1660.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| additional information | both auto-cleavage and NS3 protease activity show absolute requirement for cysteine residues 1123, 1125 and 1171 within NS3. Cysteine 922 (within NS2) is only required for NS2/3 auto-cleavage activity and histidine 1175 is only required for NS3 activity. Complete NS3 protease domain (including the C-terminal alpha-helix) is required for NS2/3 auto-cleavage, the activity of the NS3 protease is not essential | Hepacivirus C |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| minimal precursor (residues 9041206 of the hepatitis C virus polyprotein, corresponding to the C-terminal cytoplasmic domain of NS2 and the entire protease domain of NS3) introduced into vector pET23a and expressed as an insoluble protein in Escherichia coli strain BL21 (DE3) pLysS | Hepacivirus C |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| C1123A | reduces NS2/3 auto-cleavage and NS3 protease activity | Hepacivirus C |
| C1125A | reduces NS2/3 auto-cleavage and NS3 protease activity | Hepacivirus C |
| C1171A | reduces NS2/3 auto-cleavage and NS3 protease activity | Hepacivirus C |
| C1185A | has no effect on NS2/3 auto-cleavage and NS3 protease activity | Hepacivirus C |
| C922A | reduces NS2/3 auto-cleavage, but has no effect on NS3 protease activity | Hepacivirus C |
| DELTA1197 | reduces both protease activities to undetectable levels | Hepacivirus C |
| H1175A | reduces NS3 protease activity by 70%, but has no effect on NS2/3 auto-cleavage. NS3 protease activity of mutant H1175A is 3fold more sensitive to zinc chelation than wild-type in the presence of the NS4A peptide, but is indistinguishable from wild-type in the absence of the NS4A peptide | Hepacivirus C |
| H952A | totally abolishes auto-cleavage of the NS2/3 precursor | Hepacivirus C |
| L1026P/A1027P | totally abolishes auto-cleavage of the NS2/3 precursor | Hepacivirus C |
| S1165A | completely abrogates NS3 protease activity, but has no effect on NS2/3 auto-cleavage | Hepacivirus C |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 1,10-phenanthroline | inhibits NS2/3 auto-cleavage and NS3 protease activity | Hepacivirus C |  |
| EDTA | inhibits NS2/3 auto-cleavage and NS3 protease activity | Hepacivirus C | |
| additional information | EGTA and zinc metalloprotease inhibitors bestatin, phosphoramidon and thiorphan have no effect on NS2/3 auto-cleavage and NS3 protease activity. No inhibitory effect of the NS4A peptide on NS2/3 auto-cleavage, additionally the NS4A peptide does not significantly affect the sensitivity of NS2/3 autocleavage to zinc chelation, but has a marked effect on NS3 protease activity, rendering this activity approximately 3fold more resistant to zinc chelation | Hepacivirus C |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Zn2+ | both auto-cleavage and NS3 protease activity are zinc-dependent. NS2/3 auto-cleavage activity is more sensitive to zinc chelation by 1,10-phenanthroline than the NS3 protease activity | Hepacivirus C | |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 19000 | - |
NS3 fragment after autocleavage, Western blotting | Hepacivirus C |
| 35000 | - |
full length protein, Western blotting | Hepacivirus C |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Hepacivirus C | O92972 | - |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| minimal precursor (residues 9041206 of the hepatitis C virus polyprotein) purified from insoluble inclusion bodies by solubilization in 6 M guanidine hydrochloride and metal chelate resin affinity chromatography | Hepacivirus C |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| EDVVPCSMSYN + H2O | - |
Hepacivirus C | ? | - |
? | |
| additional information | NS2/3 precursor is able to auto-cleave | Hepacivirus C | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| NS2/3 protease | - |
Hepacivirus C |
| NS3 | - |
Hepacivirus C |
| NS3 protease | - |
Hepacivirus C |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.78 | - |
inhibition of NS2/3 auto-cleavage of mutant H1175A in the absence of NS4A peptide | Hepacivirus C | 1,10-phenanthroline | |
| 0.79 | - |
inhibition of NS2/3 auto-cleavage of the wild-type in the absence of NS4A peptide | Hepacivirus C | 1,10-phenanthroline | |
| 0.89 | - |
inhibition of NS2/3 auto-cleavage of the wild-type in the presence of NS4A peptide | Hepacivirus C | 1,10-phenanthroline | |
| 1.56 | - |
inhibition of mutant H1175A NS3 protease activity in the absence of NS4A peptide | Hepacivirus C | 1,10-phenanthroline | |
| 1.9 | - |
inhibition of wild-type NS3 protease activity in the absence of NS4A peptide | Hepacivirus C | 1,10-phenanthroline | |
| 2.1 | - |
inhibition of mutant H1175A NS3 protease activity in the presence of NS4A peptide | Hepacivirus C | 1,10-phenanthroline | |
| 5.9 | - |
inhibition of wild-type NS3 protease activity in the presence of NS4A peptide | Hepacivirus C | 1,10-phenanthroline | |
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