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Literature summary for 3.4.21.91 extracted from

  • Kuiper, B.D.; Slater, K.; Spellmon, N.; Holcomb, J.; Medapureddy, P.; Muzzarelli, K.M.; Yang, Z.; Ovadia, R.; Amblard, F.; Kovari, I.A.; Schinazi, R.F.; Kovari, L.C.
    Increased activity of unlinked Zika virus NS2B/NS3 protease compared to linked Zika virus protease (2017), Biochem. Biophys. Res. Commun., 492, 668-673 .
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
recombinant overexpression of His6-SUMO-tagged linked and unlinked NS3-NS2B(45-95) complex linked via G4SG4 linker in Escherichia coli strain BL21 Codon Plus (DE3) Zika virus

Protein Variants

Protein Variants Comment Organism
R95*A/R29G construction of a complex containing residues 45 to 95 of the NS2B cofactor linked via a Gly-Gly-Gly-Gly-Ser-Gly-Gly-Gly-Gly (G4SG4) linker to the NS3 protease to avoid auto-proteolysis and create the linked protease, the last arginine residue of the NS2B cofactor before the G4SG4 linker is mutated to alanine (R95*A), and arginine 29 of the NS3 protease domain is mutated to glycine (R29G) Zika virus

Inhibitors

Inhibitors Comment Organism Structure
N2-(thiophen-2-ylcarbonyl)-L-arginyl-N-[(1S)-2-amino-2-oxo-1-(4-[[4-(trifluoromethyl)benzyl]oxy]phenyl)ethyl]-L-lysinamide the compound inhibits both unlinked and linked protease with similar potency Zika virus

Organism

Organism UniProt Comment Textmining
Zika virus A0A384KRS4 genome polyprotein; ZIKV, the ZIKV isolate is from Puerto Rico, which stems from the Asian lineage and is relevant to the 2015-2016 outbreak in North and South America
-
Zika virus Puerto Rico isolate A0A384KRS4 genome polyprotein; ZIKV, the ZIKV isolate is from Puerto Rico, which stems from the Asian lineage and is relevant to the 2015-2016 outbreak in North and South America
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His6-SUMO-tagged linked and unlinked NS3-NS2B(45-95) complex linked from Escherichia coli strain BL21 Codon Plus (DE3) by nickel affinity chromatography, tag cleavage by yeast SUMO Protease 1, followed by another step of nickel affinity chromatography, and gel filtration Zika virus

Synonyms

Synonyms Comment Organism
NS2B/NS3 protease
-
Zika virus
ZIKV NS2B/NS3 protease
-
Zika virus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Zika virus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8.5
-
assay at Zika virus

Cofactor

Cofactor Comment Organism Structure
NS2B cofactor the NS2B cofactor is covalently linked to the NS3 protease domain via a Gly-Gly-Gly-Gly-Ser-Gly-Gly-Gly-Gly (G4SG4) linker Zika virus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00104
-
recombinant linked protease, pH 8.5, 37°C Zika virus N2-(thiophen-2-ylcarbonyl)-L-arginyl-N-[(1S)-2-amino-2-oxo-1-(4-[[4-(trifluoromethyl)benzyl]oxy]phenyl)ethyl]-L-lysinamide
0.00106
-
recombinant unlinked protease, pH 8.5, 37°C Zika virus N2-(thiophen-2-ylcarbonyl)-L-arginyl-N-[(1S)-2-amino-2-oxo-1-(4-[[4-(trifluoromethyl)benzyl]oxy]phenyl)ethyl]-L-lysinamide

General Information

General Information Comment Organism
additional information increased activity of unlinked Zika virus NS2B/NS3 protease compared to linked Zika virus protease. Enzyme structure homology modeling and molecular dynamics simulations of linked and unlinked protease, overview Zika virus
physiological function the ZIKV NS2B/NS3 protease is responsible for cleavage of the viral polyprotein at five sites Zika virus