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Literature summary for 3.4.21.98 extracted from

  • Thibeault, D.; Massariol, M.J.; Zhao, S.; Welchner, E.; Goudreau, N.; Gingras, R.; Llinas-Brunet, M.; White, P.W.
    Use of the fused NS4A peptide-NS3 protease domain to study the importance of the helicase domain for protease inhibitor binding to hepatitis C virus NS3-NS4A (2009), Biochemistry, 48, 744-753.
    View publication on PubMed
Search for more literature for 3.4.21.98

Activating Compound

Activating Compound Comment Organism Structure
NS4A peptide
-
 Hepacivirus C

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli BL21(DE3) cells Hepacivirus C

Protein Variants

Protein Variants Comment Organism
M485A/V524A/Q526A mutant with reduced catalytic efficiency compared to the wild type enzyme Hepacivirus C

General Stability

General Stability Organism
a short His-tag has no effect on protease activity Hepacivirus C

Inhibitors

Inhibitors Comment Organism Structure
(2R,6S,12Z,13aS,14aR,16aS)-6-[[(cyclopentyloxy)carbonyl]amino]-2-([7-methoxy-2-[2-(propan-2-ylamino)-1,3-thiazol-4-yl]quinolin-4-yl]oxy)-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine
-
 Hepacivirus C
(2S,4S)-1-((S)-2-((R)-2-cyclohexyl-2-(prop-1-en-2-ylamino)acetamido)-3,3-dimethylbutanoyl)-N-((1S,2R)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)-4-phenylpyrrolidine-2-carboxamide
-
 Hepacivirus C
(2S,6S,12Z,13aS,14aR,16aS)-6-[[(cyclopentyloxy)carbonyl]amino]-2-[4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl]-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxylic acid
-
 Hepacivirus C
BILN 2061
-
 Hepacivirus C
N-(tert-butoxycarbonyl)-3-methyl-L-valyl-(4R)-N-[(1R,2S)-1-carboxy-2-ethenylcyclopropyl]-4-([2-[2-(dimethylamino)-1,3-thiazol-4-yl]pyridin-4-yl]oxy)-L-prolinamide
-
 Hepacivirus C
N-(tert-butoxycarbonyl)-3-methyl-L-valyl-(4R)-N-[(1R,2S)-1-carboxy-2-ethenylcyclopropyl]-4-[(7-methoxy-2-phenylquinolin-4-yl)oxy]-L-prolinamide
-
 Hepacivirus C
N-acetyl-L-aspartyl-L-glutamyl-L-isoleucyl-L-valyl-(3R)-3-(benzyloxy)-L-prolyl-N-[(1S)-1-phenylethyl]-L-norleucinamide
-
 Hepacivirus C
N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4R)-N-[(1R,2R)-1-[(cyclopropylsulfonyl)carbamoyl]-2-(methylideneamino)cyclopropyl]-4-hydroxy-L-prolinamide
-
 Hepacivirus C
N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4S)-N-[(1R,2S)-1-carboxy-2-ethenylcyclopropyl]-4-phenyl-L-prolinamide
-
 Hepacivirus C

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0029
-
 anthranilyl-DDIVPAbu[C(O)-O]AMY(3-NO2)TW-OH single chain NS3 protease domain, at 23°C Hepacivirus C
0.0042
-
 anthranilyl-DDIVPAbu[C(O)-O]AMY(3-NO2)TW-OH mutant full-length protease M485A/V524A/Q562A, at 23°C Hepacivirus C

Organism

Organism UniProt Comment Textmining
Hepacivirus C
-
-
-
Hepacivirus C J
-
-
-

Purification (Commentary)

Purification (Comment) Organism
HiTrap heparin column chromatography, HiTrap SP-HP column chromatography, and Superdex 75 gel filtration Hepacivirus C

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
anthranilyl-DDIVPAbu[C(O)-O]AMY(3-NO2)TW-OH + H2O
-
 Hepacivirus C ?
-
 ?
anthranilyl-DDIVPAbu[C(O)-O]AMY(3-NO2)TW-OH + H2O
-
 Hepacivirus C J ?
-
 ?

Synonyms

Synonyms Comment Organism
NS3 protease
-
 Hepacivirus C
sc-protease single-chain NS3 protease domain Hepacivirus C

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.62
-
 anthranilyl-DDIVPAbu[C(O)-O]AMY(3-NO2)TW-OH mutant full-length protease M485A/V524A/Q562A, at 23°C Hepacivirus C
2.5
-
 anthranilyl-DDIVPAbu[C(O)-O]AMY(3-NO2)TW-OH single chain NS3 protease domain, at 23°C Hepacivirus C

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.00000062
-
 (2R,6S,12Z,13aS,14aR,16aS)-6-[[(cyclopentyloxy)carbonyl]amino]-2-([7-methoxy-2-[2-(propan-2-ylamino)-1,3-thiazol-4-yl]quinolin-4-yl]oxy)-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine wild type enzyme, at 23°C Hepacivirus C
0.0000014
-
 (2S,4S)-1-((S)-2-((R)-2-cyclohexyl-2-(prop-1-en-2-ylamino)acetamido)-3,3-dimethylbutanoyl)-N-((1S,2R)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)-4-phenylpyrrolidine-2-carboxamide wild type enzyme, at 23°C Hepacivirus C
0.0000016
-
 (2R,6S,12Z,13aS,14aR,16aS)-6-[[(cyclopentyloxy)carbonyl]amino]-2-([7-methoxy-2-[2-(propan-2-ylamino)-1,3-thiazol-4-yl]quinolin-4-yl]oxy)-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine mutant enzyme M485A/V524A/Q526A, at 23°C Hepacivirus C
0.0000028
-
 (2S,4S)-1-((S)-2-((R)-2-cyclohexyl-2-(prop-1-en-2-ylamino)acetamido)-3,3-dimethylbutanoyl)-N-((1S,2R)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)-4-phenylpyrrolidine-2-carboxamide mutant enzyme M485A/V524A/Q526A, at 23°C Hepacivirus C
0.0000095
-
 N-(tert-butoxycarbonyl)-3-methyl-L-valyl-(4R)-N-[(1R,2S)-1-carboxy-2-ethenylcyclopropyl]-4-[(7-methoxy-2-phenylquinolin-4-yl)oxy]-L-prolinamide wild type enzyme, at 23°C Hepacivirus C
0.000015
-
 N-(tert-butoxycarbonyl)-3-methyl-L-valyl-(4R)-N-[(1R,2S)-1-carboxy-2-ethenylcyclopropyl]-4-[(7-methoxy-2-phenylquinolin-4-yl)oxy]-L-prolinamide mutant enzyme M485A/V524A/Q526A, at 23°C Hepacivirus C
0.000022
-
 (2S,6S,12Z,13aS,14aR,16aS)-6-[[(cyclopentyloxy)carbonyl]amino]-2-[4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl]-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxylic acid wild type enzyme, at 23°C Hepacivirus C
0.000041
-
 N-(tert-butoxycarbonyl)-3-methyl-L-valyl-(4R)-N-[(1R,2S)-1-carboxy-2-ethenylcyclopropyl]-4-([2-[2-(dimethylamino)-1,3-thiazol-4-yl]pyridin-4-yl]oxy)-L-prolinamide wild type enzyme, at 23°C Hepacivirus C
0.000055
-
 (2S,6S,12Z,13aS,14aR,16aS)-6-[[(cyclopentyloxy)carbonyl]amino]-2-[4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl]-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxylic acid mutant enzyme M485A/V524A/Q526A, at 23°C Hepacivirus C
0.000071
-
 N-acetyl-L-aspartyl-L-glutamyl-L-isoleucyl-L-valyl-(3R)-3-(benzyloxy)-L-prolyl-N-[(1S)-1-phenylethyl]-L-norleucinamide wild type enzyme, at 23°C Hepacivirus C
0.000078
-
 N-(tert-butoxycarbonyl)-3-methyl-L-valyl-(4R)-N-[(1R,2S)-1-carboxy-2-ethenylcyclopropyl]-4-([2-[2-(dimethylamino)-1,3-thiazol-4-yl]pyridin-4-yl]oxy)-L-prolinamide mutant enzyme M485A/V524A/Q526A, at 23°C Hepacivirus C
0.00011
-
 N-acetyl-L-aspartyl-L-glutamyl-L-isoleucyl-L-valyl-(3R)-3-(benzyloxy)-L-prolyl-N-[(1S)-1-phenylethyl]-L-norleucinamide mutant enzyme M485A/V524A/Q526A, at 23°C Hepacivirus C
0.00025
-
 N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4R)-N-[(1R,2R)-1-[(cyclopropylsulfonyl)carbamoyl]-2-(methylideneamino)cyclopropyl]-4-hydroxy-L-prolinamide wild type enzyme, at 23°C Hepacivirus C
0.00041
-
 N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4R)-N-[(1R,2R)-1-[(cyclopropylsulfonyl)carbamoyl]-2-(methylideneamino)cyclopropyl]-4-hydroxy-L-prolinamide mutant enzyme M485A/V524A/Q526A, at 23°C Hepacivirus C
0.002
-
 N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4S)-N-[(1R,2S)-1-carboxy-2-ethenylcyclopropyl]-4-phenyl-L-prolinamide wild type enzyme, at 23°C Hepacivirus C
0.0036
-
 N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4S)-N-[(1R,2S)-1-carboxy-2-ethenylcyclopropyl]-4-phenyl-L-prolinamide mutant enzyme M485A/V524A/Q526A, at 23°C Hepacivirus C

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
150
-
 anthranilyl-DDIVPAbu[C(O)-O]AMY(3-NO2)TW-OH mutant full-length protease M485A/V524A/Q562A, at 23°C Hepacivirus C
840
-
 anthranilyl-DDIVPAbu[C(O)-O]AMY(3-NO2)TW-OH single chain NS3 protease domain, at 23°C Hepacivirus C