Literature summary for 3.4.21.91 extracted from

Tedbury, P.R.; Harris, M.
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.

Search for more literature for 3.4.21.91

Activating Compound

Activating Compound	Comment	Organism	Structure
additional information	auto-cleavage and NS3 protease activity show an absolute requirement for cysteine residues 1123, 1125 and 1171 within NS3, whereas 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, whereas activity of the NS3 protease is not essential	Hepacivirus C

Protein Variants

Protein Variants	Comment	Organism
C1123A	results in dramatic reductions in both auto-cleavage of the NS2/3 precursor and NS3 protease activities to levels that are close to the background of the assay	Hepacivirus C
C1125A	results in dramatic reductions in both auto-cleavage of the NS2/3 precursor and NS3 protease activities to levels that are close to the background of the assay	Hepacivirus C
C1171A	results in dramatic reductions in both auto-cleavage of the NS2/3 precursor and NS3 protease activities to levels that are close to the background of the assay	Hepacivirus C
C1185A	has no effect on either auto-cleavage of the NS2/3 precursor and NS3 protease activities	Hepacivirus C
C922A	reduces NS2/3 auto-cleavage, but has no significant effect on NS3 protease activity	Hepacivirus C
H1175A	reduces NS3 protease activity. Auto-cleavage activity is indistinguishable from wild-type	Hepacivirus C
H952A	totally abolishes auto-cleavage of the NS2/3 precursor, whereas NS3 protease activity is not abolished	Hepacivirus C
L1026P/A1027P	totally abolishes auto-cleavage of the NS2/3 precursor, whereas NS3 protease activity is not abolished	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	zinc-selective chelator, inhibits NS2/3 auto-cleavage and NS3 protease activity	Hepacivirus C
EDTA	zinc-selective chelator, inhibits NS2/3 auto-cleavage and NS3 protease activity	Hepacivirus C
additional information	EGTA or inhibitors of bacterial and mammalian metalloendopeptidases, aminopeptidase, angiotensin converting enzyme, and metalloprotease-disintegrins have no effect on NS2/3 auto-cleavage and NS3 protease activity. No inhibitory effect of the NS4A peptide on NS2/3 auto-cleavage. NS4A 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+	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
30000	-	truncated form resulting from a proteolytic cleavage near the C-terminus of the protein, immunoprecipitation	Hepacivirus C
35000	-	full-length NS3/NS2, immunoprecipitation	Hepacivirus C

Organism

Organism	UniProt	Comment	Textmining
Hepacivirus C	-	-	-

Purification (Commentary)

Purification (Comment)	Organism
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.
additional information	NS2/3 auto-cleavage and NS3 protease activity	Hepacivirus C	?	-	?

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.89	-	inhibition of NS2/3 auto-cleavage	Hepacivirus C	1,10-phenanthroline
5.9	-	inhibition of NS3 protease activity	Hepacivirus C	1,10-phenanthroline

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Release 2023.1 (January 2023)