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Literature summary for 3.6.1.1 extracted from

  • Pang, A.H.; Garzan, A.; Larsen, M.J.; McQuade, T.J.; Garneau-Tsodikova, S.; Tsodikov, O.V.
    Discovery of allosteric and selective inhibitors of inorganic pyrophosphatase from Mycobacterium tuberculosis (2016), ACS Chem. Biol., 11, 3084-3092 .
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of N-terminally His10-tagged enzyme in Escherichia coli strain BL21(DE3) Escherichia coli
recombinant expression of N-terminally His10-tagged enzyme in Escherichia coli strain BL21(DE3) Mycobacterium tuberculosis

Crystallization (Commentary)

Crystallization (Comment) Organism
purified recombinant detagged enzyme in complex with inhibitor 2,4-bis(aziridin-1-yl)-6-(1-phenylpyrrol-2-yl)-S-triazine or N2,N4-dimethyl-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine-2,4-diamine, hanging drop vapour diffusion method, mixing of 7 mg/ml protein in 40 mM Tris-HCl pH 8.0, 100 mM NaCl, and 2 mM 2-mercaptoethanol, with reservoir solution containing 0.1 M HEPES pH 7.5, 1.6 M NaH2PO4, and 0.2 M KH2PO4, or 0.1 M HEPES pH 7.75, 1.4 M KH2PO4, and 2 mM CaCl2, respectively, 22°C, overnight, X-ray diffraction structure determination and analysis at 2.65 A and 2.45 A resolution, respectively. 2,4-Bis(aziridin-1-yl)-6-(1-phenylpyrrol-2-yl)-S-triazine is co-crystallized, while N2,N4-dimethyl-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine-2,4-diamine is bound by soaking Mycobacterium tuberculosis

Inhibitors

Inhibitors Comment Organism Structure
1,1'-[6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine-2,4-diyl]bis(azepane)
-
Escherichia coli
1,1'-[6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine-2,4-diyl]bis(azepane)
-
Mycobacterium tuberculosis
1,1'-[6-[1-(3,5-dimethylphenyl)-1H-pyrrol-2-yl]-1,3,5-triazine-2,4-diyl]bis(azepane)
-
Escherichia coli
1,1'-[6-[1-(3,5-dimethylphenyl)-1H-pyrrol-2-yl]-1,3,5-triazine-2,4-diyl]bis(azepane)
-
Mycobacterium tuberculosis
1-(2-phenylethyl)-1H-pyrrole
-
Escherichia coli
1-(2-phenylethyl)-1H-pyrrole
-
Mycobacterium tuberculosis
1-(3,5-dimethylphenyl)-1H-pyrrole
-
Escherichia coli
1-(3,5-dimethylphenyl)-1H-pyrrole
-
Mycobacterium tuberculosis
1-(3-phenylpropyl)-1H-pyrrole
-
Escherichia coli
1-(3-phenylpropyl)-1H-pyrrole
-
Mycobacterium tuberculosis
1-benzyl-1H-pyrrole
-
Escherichia coli
1-benzyl-1H-pyrrole
-
Mycobacterium tuberculosis
1-cyclohexyl-1H-pyrrole
-
Escherichia coli
1-cyclohexyl-1H-pyrrole
-
Mycobacterium tuberculosis
1-[4-(1-benzyl-1H-tetrazol-5-yl)-4-[(prop-2-yn-1-yl)amino]piperidin-1-yl]-3-(3-methyl-3H-diazirin-3-yl)propan-1-one
-
Escherichia coli
1-[4-(1-benzyl-1H-tetrazol-5-yl)-4-[(prop-2-yn-1-yl)amino]piperidin-1-yl]-3-(3-methyl-3H-diazirin-3-yl)propan-1-one
-
Mycobacterium tuberculosis
1-[4-chloro-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazin-2-yl]azepane
-
Escherichia coli
1-[4-chloro-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazin-2-yl]azepane
-
Mycobacterium tuberculosis
10-bromo-3-(butylsulfanyl)-6-(thiophen-2-yl)-6,7-dihydro[1,2,4]triazino[5,6-d][3,1]benzoxazepine
-
Escherichia coli
10-bromo-3-(butylsulfanyl)-6-(thiophen-2-yl)-6,7-dihydro[1,2,4]triazino[5,6-d][3,1]benzoxazepine
-
Mycobacterium tuberculosis
2,4-bis(aziridin-1-yl)-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine
-
Escherichia coli
2,4-bis(aziridin-1-yl)-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine
-
Mycobacterium tuberculosis
2,4-bis(aziridin-1-yl)-6-(1-phenylpyrrol-2-yl)-S-triazine allosteric inhibitor Escherichia coli
2,4-bis(aziridin-1-yl)-6-(1-phenylpyrrol-2-yl)-S-triazine allosteric inhibitor Mycobacterium tuberculosis
2,4-bis(morpholin-4-yl)-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine
-
Escherichia coli
2,4-bis(morpholin-4-yl)-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine
-
Mycobacterium tuberculosis
2,4-bis[(oxiran-2-yl)methoxy]-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine
-
Escherichia coli
2,4-bis[(oxiran-2-yl)methoxy]-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine
-
Mycobacterium tuberculosis
2,4-dichloro-6-(1-cyclohexyl-1H-pyrrol-2-yl)-1,3,5-triazine
-
Escherichia coli
2,4-dichloro-6-(1-cyclohexyl-1H-pyrrol-2-yl)-1,3,5-triazine
-
Mycobacterium tuberculosis
2,4-dichloro-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine
-
Escherichia coli
2,4-dichloro-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine
-
Mycobacterium tuberculosis
2,4-dichloro-6-[1-(2-phenylethyl)-1H-pyrrol-2-yl]-1,3,5-triazine
-
Escherichia coli
2,4-dichloro-6-[1-(2-phenylethyl)-1H-pyrrol-2-yl]-1,3,5-triazine
-
Mycobacterium tuberculosis
2,4-dichloro-6-[1-(3,5-dimethylphenyl)-1H-pyrrol-2-yl]-1,3,5-triazine
-
Escherichia coli
2,4-dichloro-6-[1-(3,5-dimethylphenyl)-1H-pyrrol-2-yl]-1,3,5-triazine
-
Mycobacterium tuberculosis
2,4-dichloro-6-[1-(3-phenylpropyl)-1H-pyrrol-2-yl]-1,3,5-triazine
-
Escherichia coli
2,4-dichloro-6-[1-(3-phenylpropyl)-1H-pyrrol-2-yl]-1,3,5-triazine
-
Mycobacterium tuberculosis
2-(1-benzyl-1H-pyrrol-2-yl)-4,6-dichloro-1,3,5-triazine
-
Escherichia coli
2-(1-benzyl-1H-pyrrol-2-yl)-4,6-dichloro-1,3,5-triazine
-
Mycobacterium tuberculosis
2-(1-phenyl-1H-pyrrol-2-yl)-4,6-di(piperidin-1-yl)-1,3,5-triazine
-
Escherichia coli
2-(1-phenyl-1H-pyrrol-2-yl)-4,6-di(piperidin-1-yl)-1,3,5-triazine
-
Mycobacterium tuberculosis
2-(1-phenyl-1H-pyrrol-2-yl)-4,6-di(pyrrolidin-1-yl)-1,3,5-triazine
-
Escherichia coli
2-(1-phenyl-1H-pyrrol-2-yl)-4,6-di(pyrrolidin-1-yl)-1,3,5-triazine
-
Mycobacterium tuberculosis
2-chloro-4-(methanesulfonyl)benzoic acid
-
Escherichia coli
2-chloro-4-(methanesulfonyl)benzoic acid
-
Mycobacterium tuberculosis
2-methyl-4-(3-phenyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)quinoline
-
Escherichia coli
2-methyl-4-(3-phenyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)quinoline
-
Mycobacterium tuberculosis
2-[(5-cyanopyridin-2-yl)(methyl)amino]ethyl 4-methyl-1,2,3-thiadiazole-5-carboxylate
-
Escherichia coli
2-[(5-cyanopyridin-2-yl)(methyl)amino]ethyl 4-methyl-1,2,3-thiadiazole-5-carboxylate
-
Mycobacterium tuberculosis
2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethyl 2-(4-methoxyphenyl)-3-methyl-4-oxo-1,2,3,3a,4,9b-hexahydro[1]benzopyrano[3,4-b]pyrrole-1-carboxylate
-
Escherichia coli
2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethyl 2-(4-methoxyphenyl)-3-methyl-4-oxo-1,2,3,3a,4,9b-hexahydro[1]benzopyrano[3,4-b]pyrrole-1-carboxylate
-
Mycobacterium tuberculosis
3-(butylsulfanyl)-6-(5-methylfuran-2-yl)-6,7-dihydro[1,2,4]triazino[5,6-d][3,1]benzoxazepine
-
Escherichia coli
3-(butylsulfanyl)-6-(5-methylfuran-2-yl)-6,7-dihydro[1,2,4]triazino[5,6-d][3,1]benzoxazepine
-
Mycobacterium tuberculosis
4-(1-benzyl-1H-pyrrol-2-yl)-N,N-dibutyl-6-chloro-1,3,5-triazin-2-amine
-
Escherichia coli
4-(1-benzyl-1H-pyrrol-2-yl)-N,N-dibutyl-6-chloro-1,3,5-triazin-2-amine
-
Mycobacterium tuberculosis
4-(azepan-1-yl)-6-(1-benzyl-1H-pyrrol-2-yl)-N,N-dibutyl-1,3,5-triazin-2-amine
-
Escherichia coli
4-(azepan-1-yl)-6-(1-benzyl-1H-pyrrol-2-yl)-N,N-dibutyl-1,3,5-triazin-2-amine
-
Mycobacterium tuberculosis
4-(azepan-1-yl)-N,N-dibutyl-6-(1-cyclohexyl-1H-pyrrol-2-yl)-1,3,5-triazin-2-amine
-
Escherichia coli
4-(azepan-1-yl)-N,N-dibutyl-6-(1-cyclohexyl-1H-pyrrol-2-yl)-1,3,5-triazin-2-amine
-
Mycobacterium tuberculosis
4-(azepan-1-yl)-N,N-dibutyl-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazin-2-amine
-
Escherichia coli
4-(azepan-1-yl)-N,N-dibutyl-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazin-2-amine
-
Mycobacterium tuberculosis
4-(azepan-1-yl)-N,N-dibutyl-6-[1-(2-phenylethyl)-1H-pyrrol-2-yl]-1,3,5-triazin-2-amine pecies-specific inhibitor Escherichia coli
4-(azepan-1-yl)-N,N-dibutyl-6-[1-(2-phenylethyl)-1H-pyrrol-2-yl]-1,3,5-triazin-2-amine pecies-specific inhibitor Mycobacterium tuberculosis
4-(azepan-1-yl)-N,N-dibutyl-6-[1-(3,5-dimethylphenyl)-1H-pyrrol-2-yl]-1,3,5-triazin-2-amine
-
Escherichia coli
4-(azepan-1-yl)-N,N-dibutyl-6-[1-(3,5-dimethylphenyl)-1H-pyrrol-2-yl]-1,3,5-triazin-2-amine
-
Mycobacterium tuberculosis
4-(azepan-1-yl)-N,N-dibutyl-6-[1-(3-phenylpropyl)-1H-pyrrol-2-yl]-1,3,5-triazin-2-amine
-
Escherichia coli
4-(azepan-1-yl)-N,N-dibutyl-6-[1-(3-phenylpropyl)-1H-pyrrol-2-yl]-1,3,5-triazin-2-amine
-
Mycobacterium tuberculosis
4-(azepan-1-yl)-N,N-dihexyl-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazin-2-amine
-
Escherichia coli
4-(azepan-1-yl)-N,N-dihexyl-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazin-2-amine
-
Mycobacterium tuberculosis
4-(azepan-1-yl)-N,N-dimethyl-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazin-2-amine
-
Escherichia coli
4-(azepan-1-yl)-N,N-dimethyl-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazin-2-amine
-
Mycobacterium tuberculosis
4-chloro-N,N-dihexyl-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazin-2-amine
-
Escherichia coli
4-chloro-N,N-dihexyl-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazin-2-amine
-
Mycobacterium tuberculosis
5-bromo-1,3-dimethylpyrimidine-2,4(1H,3H)-dione
-
Escherichia coli
5-bromo-1,3-dimethylpyrimidine-2,4(1H,3H)-dione
-
Mycobacterium tuberculosis
6-(1-benzyl-1H-pyrrol-2-yl)-N2,N2-dibutyl-N4,N4-dihexyl-1,3,5-triazine-2,4-diamine
-
Escherichia coli
6-(1-benzyl-1H-pyrrol-2-yl)-N2,N2-dibutyl-N4,N4-dihexyl-1,3,5-triazine-2,4-diamine
-
Mycobacterium tuberculosis
6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine-2,4-diamine
-
Escherichia coli
6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine-2,4-diamine
-
Mycobacterium tuberculosis
dipropan-2-yl [(E)-(2-benzoylhydrazinylidene)(hydroxyamino)methyl]phosphonate
-
Escherichia coli
dipropan-2-yl [(E)-(2-benzoylhydrazinylidene)(hydroxyamino)methyl]phosphonate
-
Mycobacterium tuberculosis
methyl 2-(4-methoxyphenyl)-3-methyl-4-oxo-3,4-dihydro[1]benzopyrano[3,4-b]pyrrole-1-carboxylate
-
Escherichia coli
methyl 2-(4-methoxyphenyl)-3-methyl-4-oxo-3,4-dihydro[1]benzopyrano[3,4-b]pyrrole-1-carboxylate
-
Mycobacterium tuberculosis
methyl 3-amino-4-(propane-2-sulfonyl)thiophene-2-carboxylate
-
Escherichia coli
methyl 3-amino-4-(propane-2-sulfonyl)thiophene-2-carboxylate
-
Mycobacterium tuberculosis
methyl 3-benzyl-2-(4-methoxyphenyl)-4-oxo-3,4-dihydro[1]benzopyrano[3,4-b]pyrrole-1-carboxylate
-
Escherichia coli
methyl 3-benzyl-2-(4-methoxyphenyl)-4-oxo-3,4-dihydro[1]benzopyrano[3,4-b]pyrrole-1-carboxylate
-
Mycobacterium tuberculosis
additional information discovery and synthesis of analogues of lead compound allosteric inhibitor (2,4-bis(aziridin-1-yl)-6-(1-phenylpyrrol-2-yl)-S-triazine) as inhibitors of bacterial PPiases Escherichia coli
additional information discovery and synthesis of analogues of lead compound allosteric inhibitor (2,4-bis(aziridin-1-yl)-6-(1-phenylpyrrol-2-yl)-S-triazine) as inhibitors of bacterial PPiases Mycobacterium tuberculosis
N'-(2,4,5-trichlorobenzene-1-sulfonyl)pyridine-3-carbohydrazide
-
Escherichia coli
N'-(2,4,5-trichlorobenzene-1-sulfonyl)pyridine-3-carbohydrazide
-
Mycobacterium tuberculosis
N'-(2,6-dichlorophenyl)-5-nitrofuran-2-carbohydrazide
-
Escherichia coli
N'-(2,6-dichlorophenyl)-5-nitrofuran-2-carbohydrazide
-
Mycobacterium tuberculosis
N,N-dibutyl-4-chloro-6-(1-cyclohexyl-1H-pyrrol-2-yl)-1,3,5-triazin-2-amine
-
Escherichia coli
N,N-dibutyl-4-chloro-6-(1-cyclohexyl-1H-pyrrol-2-yl)-1,3,5-triazin-2-amine
-
Mycobacterium tuberculosis
N,N-dibutyl-4-chloro-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazin-2-amine
-
Escherichia coli
N,N-dibutyl-4-chloro-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazin-2-amine
-
Mycobacterium tuberculosis
N,N-dibutyl-4-chloro-6-[1-(2-phenylethyl)-1H-pyrrol-2-yl]-1,3,5-triazin-2-amine
-
Escherichia coli
N,N-dibutyl-4-chloro-6-[1-(2-phenylethyl)-1H-pyrrol-2-yl]-1,3,5-triazin-2-amine
-
Mycobacterium tuberculosis
N,N-dibutyl-4-chloro-6-[1-(3,5-dimethylphenyl)-1H-pyrrol-2-yl]-1,3,5-triazin-2-amine
-
Escherichia coli
N,N-dibutyl-4-chloro-6-[1-(3,5-dimethylphenyl)-1H-pyrrol-2-yl]-1,3,5-triazin-2-amine
-
Mycobacterium tuberculosis
N,N-dibutyl-4-chloro-6-[1-(3-phenylpropyl)-1H-pyrrol-2-yl]-1,3,5-triazin-2-amine
-
Escherichia coli
N,N-dibutyl-4-chloro-6-[1-(3-phenylpropyl)-1H-pyrrol-2-yl]-1,3,5-triazin-2-amine
-
Mycobacterium tuberculosis
N-(2-[[(4-chlorophenyl)methyl]sulfanyl]ethyl)-3-methylbut-2-enamide
-
Escherichia coli
N-(2-[[(4-chlorophenyl)methyl]sulfanyl]ethyl)-3-methylbut-2-enamide
-
Mycobacterium tuberculosis
N-(3-chlorophenyl)-N'-(5-[[(4-chlorophenyl)sulfanyl]methyl]furan-2-yl)urea
-
Escherichia coli
N-(3-chlorophenyl)-N'-(5-[[(4-chlorophenyl)sulfanyl]methyl]furan-2-yl)urea
-
Mycobacterium tuberculosis
N-[4-[(3,5-dichlorophenyl)sulfamoyl]phenyl]acetamide
-
Escherichia coli
N-[4-[(3,5-dichlorophenyl)sulfamoyl]phenyl]acetamide
-
Mycobacterium tuberculosis
N2,N2,N4,N4-tetramethyl-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine-2,4-diamine
-
Escherichia coli
N2,N2,N4,N4-tetramethyl-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine-2,4-diamine
-
Mycobacterium tuberculosis
N2,N4-dimethyl-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine-2,4-diamine
-
Escherichia coli
N2,N4-dimethyl-6-(1-phenyl-1H-pyrrol-2-yl)-1,3,5-triazine-2,4-diamine
-
Mycobacterium tuberculosis
[1,1'-biphenyl]-2,2'-dicarbonitrile
-
Escherichia coli
[1,1'-biphenyl]-2,2'-dicarbonitrile
-
Mycobacterium tuberculosis

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information Michaelis-Menten kinetics Escherichia coli
additional information
-
additional information Michaelis-Menten kinetics Mycobacterium tuberculosis

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Escherichia coli
Mg2+ required Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
diphosphate + H2O Escherichia coli
-
2 phosphate
-
?
diphosphate + H2O Mycobacterium tuberculosis
-
2 phosphate
-
?

Organism

Organism UniProt Comment Textmining
Escherichia coli P0A7A9
-
-
Mycobacterium tuberculosis Q3LIE5
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His10-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, gel filtration, tag cleavage, and again gel filtration Escherichia coli
recombinant His10-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, gel filtration, tag cleavage, and again gel filtration Mycobacterium tuberculosis

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
diphosphate + H2O
-
Escherichia coli 2 phosphate
-
?
diphosphate + H2O
-
Mycobacterium tuberculosis 2 phosphate
-
?

Synonyms

Synonyms Comment Organism
EcPPiase
-
Escherichia coli
inorganic pyrophosphatase
-
Escherichia coli
inorganic pyrophosphatase
-
Mycobacterium tuberculosis
MtPPiase
-
Mycobacterium tuberculosis
PPias
-
Escherichia coli
PPias
-
Mycobacterium tuberculosis

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Escherichia coli
37
-
assay at Mycobacterium tuberculosis

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Escherichia coli
7.5
-
assay at Mycobacterium tuberculosis

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.011
-
4-(azepan-1-yl)-N,N-dibutyl-6-[1-(2-phenylethyl)-1H-pyrrol-2-yl]-1,3,5-triazin-2-amine recombinant enzyme, pH 7.5, 37°C Escherichia coli
0.011
-
4-(azepan-1-yl)-N,N-dibutyl-6-[1-(2-phenylethyl)-1H-pyrrol-2-yl]-1,3,5-triazin-2-amine recombinant enzyme, pH 7.5, 37°C Mycobacterium tuberculosis