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Literature summary for 3.4.22.28 extracted from

  • Huitema, C.; Zhang, J.; Yin, J.; James, M.N.; Vederas, J.C.; Eltis, L.D.
    Heteroaromatic ester inhibitors of hepatitis A virus 3C proteinase: Evaluation of mode of action (2008), Bioorg. Med. Chem., 16, 5761-5777.
    View publication on PubMed
Search for more literature for 3.4.22.28

Cloned(Commentary)

Cloned (Comment) Organism
the 3Cpro mutant is produced heterologously using Escherichia coli BL21(DE3) pLysS containing pHAV-3CEX Hepatovirus A

Protein Variants

Protein Variants Comment Organism
C24S substitution of the non-essential surface cysteine residue in the C24S variant prevents intermolecular disulfide bond formation Hepatovirus A

Inhibitors

Inhibitors Comment Organism Structure
(5-bromopyridin-3-yl)methyl furan-2-carboxylate 67% inhibition at 10 microM inhibitor concentration Hepatovirus A
(E)-5-chloropyridin-3-yl 3-(furan-2-yl)acrylate 83% inhibition at 10 microM inhibitor concentration, above 90% inhibition at 1 microM inhibitor concentration, 43% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
2-chloropyridin-3-yl thiophene-2-carboxylate 11% inhibition at 10 microM inhibitor concentration Hepatovirus A
2-methylpyridin-3-yl thiophene-2-carboxylate below 10% inhibition at 10 microM inhibitor concentration, below 10% inhibition at 1 microM inhibitor concentration Hepatovirus A
2-pyridin-3-yl-1-thiophen-2-ylethanone 10% inhibition at 10 microM inhibitor concentration Hepatovirus A
3-chloro-5-(furan-2-ylmethoxy)pyridine below 10% inhibition at 10 microM inhibitor concentration Hepatovirus A
3-chlorophenyl furan-2-carboxylate 11% inhibition at 10 microM inhibitor concentration Hepatovirus A
5-bromopyridin-3-yl furan-3-carboxylate inhibition not detected at 10 microM inhibitor concentration, above 90% inhibition at 1 microM inhibitor concentration, 87% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 1,3-thiazole-4-carboxylate above 90% inhibition at 10 microM inhibitor concentration, 85% inhibition at 1 microM inhibitor concentration, 37% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 1-benzofuran-2-carboxylate above 90% inhibition at 10 microM inhibitor concentration, above 90% inhibition at 1 microM inhibitor concentration, below 10% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 1-benzothiophene-2-carboxylate above 90% inhibition at 10 microM inhibitor concentration, 47% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 1-naphthoate above 90% inhibition at 10 microM inhibitor concentration, 30% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 1H-benzo[d]imidazole-5-carboxylate 82% inhibition at 10 microM inhibitor concentration, 75% inhibition at 1 microM inhibitor concentration, 32% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 1H-benzo[d][1,2,3]triazole-5-carboxylate above 90% inhibition at 10 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 1H-imidazole-4-carboxylate 33% inhibition at 10 microM inhibitor concentration, 47% inhibition at 1 microM inhibitor concentration, 34% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 1H-indole-2-carboxylate 80% inhibition at 10 microM inhibitor concentration, 58% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 1H-indole-3-carboxylate 13% inhibition at 10 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 1H-indole-5-carboxylate 87% inhibition at 10 microM inhibitor concentration, 60% inhibition at 1 microM inhibitor concentration, 22% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 1H-pyrazole-4-carboxylate 56% inhibition at 10 microM inhibitor concentration, 21% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 2,6-dichloro-5-fluoronicotinate 44% inhibition at 10 microM inhibitor concentration, 19% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 2-chlorobenzoate above 90% inhibition at 10 microM inhibitor concentration, 67% inhibition at 1 microM inhibitor concentration, 23% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 2-methoxybenzoate 85% inhibition at 10 microM inhibitor concentration, 57% inhibition at 1 microM inhibitor concentration, below 10% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 2-methylbenzoate 82% inhibition at 10 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 2-naphthoate 23% inhibition at 10 microM inhibitor concentration, 35% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 2-nitrobenzoate above 90% inhibition at 10 microM inhibitor concentration, 24% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 2-oxo-2H-chromene-3-carboxylate 75% inhibition at 10 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 3,4-dimethoxybenzoate 59% inhibition at 10 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 3-acetoxybenzoate above 90% inhibition at 10 microM inhibitor concentration, 27% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 3-chlorobenzoate 29% inhibition at 10 microM inhibitor concentration, 50% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 3-methylbenzoate 63% inhibition at 10 microM inhibitor concentration, 32% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 3-methylthiophene-2-carboxylate below 10% inhibition at 10 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 4-(diethylamino)benzoate 64% inhibition at 10 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 4-(dimethylamino)benzoate above 90% inhibition at 10 microM inhibitor concentration, above 90% inhibition at 1 microM inhibitor concentration, 20% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 4-(methylamino)benzoate 82% inhibition at 10 microM inhibitor concentration, below 10% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 4-aminobenzoate above 90% inhibition at 10 microM inhibitor concentration, 26% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 4-chloro-2-hydroxybenzoate above 90% inhibition at 10 microM inhibitor concentration, 59% inhibition at 1 microM inhibitor concentration, 10% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 4-fluorobenzoate above 90% inhibition at 10 microM inhibitor concentration, 45% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 4-hydroxy-7-(trifluoromethyl)quinoline-3-carboxylate below 10% inhibition at 10 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 4-methoxybenzoate 85% inhibition at 10 microM inhibitor concentration; above 90% inhibition at 10 microM inhibitor concentration, 50% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 4-methylbenzoate 77% inhibition at 10 microM inhibitor concentration, 70% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 4-sulfamoylbenzoate 64% inhibition at 10 microM inhibitor concentration, 57% inhibition at 1 microM inhibitor concentration, below 10% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 5-(2-(trifluoromethyl)phenyl)furan-2-carboxylate above 90% inhibition at 10 microM inhibitor concentration, below 10% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 5-(2-chloro-5-(trifluoromethyl)phenyl)furan-2-carboxylate 76% inhibition at 10 microM inhibitor concentration, 36% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 5-(2-nitrophenyl)furan-2-carboxylate 37% inhibition at 10 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 5-(3-nitrophenyl)furan-2-carboxylate Inhibition not detected at 10 microM, 1 microM and 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 5-(4-chloro-2-nitrophenyl)furan-2-carboxylate 40% inhibition at 10 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 5-(4-chlorophenyl)furan-2-carboxylate above 90% inhibition at 10 microM inhibitor concentration, 36% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 5-bromofuran-2-carboxylate above 90% inhibition at 10 microM inhibitor concentration, 54% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 5-methyl-3-phenylisoxazole-4-carboxylate below 10% inhibition at 10 microM inhibitor concentration, below 10% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 5-methylthiophene-2-carboxylate above 90% inhibition at 10 microM inhibitor concentration, 24% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl 5-nitro-1H-pyrazole-3-carboxylate 54% inhibition at 10 microM inhibitor concentration, 69% inhibition at 1 microM inhibitor concentration, 53% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl benzoate above 90% inhibition at 10 microM inhibitor concentration, above 90% inhibition at 1 microM inhibitor concentration, below 10% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl benzo[d]thiazole-6-carboxylate 74% inhibition at 10 microM inhibitor concentration, 54% inhibition at 1 microM inhibitor concentration, 27% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl benzo[d][1,3]dioxole-5-carboxylate above 90% inhibition at 10 microM inhibitor concentration, 11% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl biphenyl-4-carboxylate 39% inhibition at 10 microM inhibitor concentration, 23% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl cinnamate above 90% inhibition at 10 microM inhibitor concentration, 53% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl cyclohexanecarboxylate 81% inhibition at 10 microM inhibitor concentration, 32% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl furan-2-carboxylate above 90% inhibition at 10 microM inhibitor concentration, above 90%% inhibition at 1 microM inhibitor concentration, 49% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl furan-3-carboxylate above 90% inhibition at 10 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl isonicotinate 37% inhibition at 10 microM inhibitor concentration, 34% inhibition at 1 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl pyrazine-2-carboxylate 22% inhibition at 10 microM inhibitor concentration Hepatovirus A
5-chloropyridin-3-yl thiophene-2-carboxylate 93% inhibition at 10 microM inhibitor concentration; above 90% inhibition at 10 microM inhibitor concentration, above 90% inhibition at 1 microM inhibitor concentration, 50% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
5-methylpyridin-2-yl thiophene-2-carboxylate 12% inhibition at 10 microM inhibitor concentration Hepatovirus A
6-chloropyridin-2-yl thiophene-2-carboxylate 16% inhibition at 10 microM inhibitor concentration Hepatovirus A
6-chloropyridin-3-yl 1H-pyrrole-2-carboxylate 92% inhibition at 10 microM inhibitor concentration, below 10% inhibition at 1 microM inhibitor concentration, below 10% inhibition at 0.25 microM inhibitor concentration Hepatovirus A
6-chloropyridin-3-yl thiophene-2-carboxylate 25% inhibition at 10 microM inhibitor concentration Hepatovirus A
6-methyl-2-nitropyridin-3-yl thiophene-2-carboxylate 14% inhibition at 10 microM inhibitor concentration Hepatovirus A
6-methylpyridin-2-yl thiophene-2-carboxylate 91% inhibition at 10 microM inhibitor concentration, below 10% inhibition at 1 microM inhibitor concentration Hepatovirus A
6-methylpyridin-3-yl thiophene-2-carboxylate 23% inhibition at 10 microM inhibitor concentration Hepatovirus A
furan-2-yl pyridine-3-carboxylate above 90% inhibition at 10 microM inhibitor concentration Hepatovirus A
N-(2-chloropyridin-3-yl)thiophene-2-carboxamide below 10% inhibition at 10 microM inhibitor concentration Hepatovirus A
N-(5-chloropyridin-2-yl)thiophene-2-carboxamide below 10% inhibition at 10 microM inhibitor concentration Hepatovirus A
N-(5-fluoropyridin-2-yl)thiophene-2-carboxamide below 10% inhibition at 10 microM inhibitor concentration Hepatovirus A
N-(6-chloropyridin-3-yl)thiophene-2-carboxamide 19% inhibition at 10 microM inhibitor concentration Hepatovirus A
N-pyridin-2-ylthiophene-2-carboxamide below 10% inhibition at 10 microM inhibitor concentration Hepatovirus A
N-pyridin-3-ylthiophene-2-carboxamide below 10% inhibition at 10 microM inhibitor concentration Hepatovirus A
N-pyridin-3-ylthiophene-2-sulfonamide below 10% inhibition at 10 microM inhibitor concentration Hepatovirus A
N-pyridin-4-ylthiophene-2-carboxamide below 10% inhibition at 10 microM inhibitor concentration Hepatovirus A
pyridin-2-yl thiophene-2-carboxylate 89% inhibition at 10 microM inhibitor concentration, 8% inhibition at 1 microM inhibitor concentration Hepatovirus A
pyridin-3-yl thiophene-2-carboxylate 83% inhibition at 10 microM inhibitor concentration, 21% inhibition at 1 microM inhibitor concentration Hepatovirus A
pyridin-4-yl thiophene-2-carboxylate below 10% inhibition at 10 microM inhibitor concentration, 10% inhibition at 1 microM inhibitor concentration Hepatovirus A

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.00012
-
 5-bromopyridin-3-yl furan-3-carboxylate
-
 Hepatovirus A
0.00018
-
 (E)-5-chloropyridin-3-yl 3-(furan-2-yl)acrylate
-
 Hepatovirus A
0.00024
-
 5-chloropyridin-3-yl furan-2-carboxylate
-
 Hepatovirus A

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
23880
-
 wild type 3C proteinase, determined by MALDI-TOF mass spectrometry Hepatovirus A
23970
-
 wild type 3C proteinase in complex with inhibitor compound 24, determined by MALDI-TOF mass spectrometry Hepatovirus A

Organism

Organism UniProt Comment Textmining
Hepatovirus A
-
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant enzyme is purified by ion exchange chromatography Hepatovirus A

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(E)-5-chloropyridin-3-yl 3-(furan-2-yl)acrylate + H2O slowly turned over Hepatovirus A ?
-
 ?
5-bromopyridin-3-yl furan-3-carboxylate + H2O slowly turned over Hepatovirus A ?
-
 ?
5-chloropyridin-3-yl furan-2-carboxylate + H2O slowly turned over Hepatovirus A ?
-
 ?
abz-SVTLQSGY(NO2)R + H2O fluorogenic substrate Hepatovirus A ?
-
 ?
acetyl-ELRTQSFS-NH2 + H2O
-
 Hepatovirus A ?
-
 ?
dabcyl-GLRTQSND(EDANS)G + H2O fluorogenic substrate Hepatovirus A ?
-
 ?

Synonyms

Synonyms Comment Organism
3C proteinase
-
 Hepatovirus A
3Cpro
-
 Hepatovirus A

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Hepatovirus A

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.00025
-
 (E)-5-chloropyridin-3-yl 3-(furan-2-yl)acrylate
-
 Hepatovirus A
0.0011
-
 5-chloropyridin-3-yl furan-2-carboxylate
-
 Hepatovirus A
0.00119
-
 5-bromopyridin-3-yl furan-3-carboxylate
-
 Hepatovirus A

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Hepatovirus A

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000053
-
 0.1 M potassium phosphate, 2 mM EDTA, pH 7.5, 100 nM proteinase, 37°C Hepatovirus A 5-bromopyridin-3-yl furan-3-carboxylate
0.00014
-
 0.1 M potassium phosphate, 2 mM EDTA, pH 7.5, 100 nM proteinase, 37°C Hepatovirus A (E)-5-chloropyridin-3-yl 3-(furan-2-yl)acrylate
0.00025
-
 0.1 M potassium phosphate, 2 mM EDTA, pH 7.5, 100 nM proteinase, 37°C Hepatovirus A 5-chloropyridin-3-yl 5-nitro-1H-pyrazole-3-carboxylate
0.000338
-
 0.1 M potassium phosphate, 2 mM EDTA, pH 7.5, 100 nM proteinase, 37°C Hepatovirus A 5-chloropyridin-3-yl furan-2-carboxylate
0.00047
-
 0.1 M potassium phosphate, 2 mM EDTA, pH 7.5, 100 nM proteinase, 37°C Hepatovirus A 5-chloropyridin-3-yl thiophene-2-carboxylate
0.0012
-
 0.1 M potassium phosphate, 2 mM EDTA, pH 7.5, 100 nM proteinase, 37°C Hepatovirus A 5-chloropyridin-3-yl 5-bromofuran-2-carboxylate