Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary extracted from

  • Gudzera, O.I.; Golub, A.G.; Bdzhola, V.G.; Volynets, G.P.; Kovalenko, O.P.; Boyarshin, K.S.; Yaremchuk, A.D.; Protopopov, M.V.; Yarmoluk, S.M.; Tukalo, M.A.
    Identification of Mycobacterium tuberculosis leucyl-tRNA synthetase (LeuRS) inhibitors among the derivatives of 5-phenylamino-2H-[1,2,4]triazin-3-one (2016), J. Enzyme Inhib. Med. Chem., 31, 201-207 .
    View publication on PubMed

Application

EC Number Application Comment Organism
6.1.1.4 drug development leucyl-tRNA synthetase (LeuRS) is an attractive therapeutic target and a target for development of drugs Mycobacterium tuberculosis

Cloned(Commentary)

EC Number Cloned (Comment) Organism
6.1.1.4 gene LARS, recombinant expression of C-terminally His-tagged enzyme in Escherichia coli strain Rosetta (DE3) Homo sapiens
6.1.1.4 gene leuS, recombinant expression of His-tagged enzyme in Escherichia coli strain Rosetta (DE3) Mycobacterium tuberculosis

Inhibitors

EC Number Inhibitors Comment Organism Structure
6.1.1.4 2-(2,5-dimethylanilino)-5,6,7,8-tetrahydroquinazolin-4(3H)-one residual activity compared to wild-type enzyme is 71% Mycobacterium tuberculosis
6.1.1.4 2-(2-hydroxy-5-methylanilino)-3,5,6,7-tetrahydro-4H-cyclopenta[d]pyrimidin-4-one residual activity compared to wild-type enzyme is 40% Mycobacterium tuberculosis
6.1.1.4 2-(2-hydroxy-5-methylanilino)-6-propylpyrimidin-4(3H)-one residual activity compared to wild-type enzyme is 93% Mycobacterium tuberculosis
6.1.1.4 2-(2-hydroxy-5-methylanilino)quinazolin-4(3H)-one residual activity compared to wild-type enzyme is 26% Mycobacterium tuberculosis
6.1.1.4 2-(2-hydroxyanilino)-6-methylpyrimidin-4(3H)-one residual activity compared to wild-type enzyme is 42% Mycobacterium tuberculosis
6.1.1.4 2-(2-hydroxyanilino)pyrimidin-4(3H)-one residual activity compared to wild-type enzyme is 37% Mycobacterium tuberculosis
6.1.1.4 2-(2-hydroxyanilino)quinazolin-4(3H)-one residual activity compared to wild-type enzyme is 36% Mycobacterium tuberculosis
6.1.1.4 2-(3-hydroxy-4-methylanilino)-6-propylpyrimidin-4(3H)-one residual activity compared to wild-type enzyme is 36% Mycobacterium tuberculosis
6.1.1.4 2-(3-hydroxyanilino)-6-methylpyrimidin-4(3H)-one residual activity compared to wild-type enzyme is 39% Mycobacterium tuberculosis
6.1.1.4 2-(3-hydroxyanilino)quinazolin-4(3H)-one residual activity compared to wild-type enzyme is 26% Mycobacterium tuberculosis
6.1.1.4 2-(4-hydroxy-2-methylanilino)-5,6,7,8-tetrahydroquinazolin-4(3H)-one residual activity compared to wild-type enzyme is 70% Mycobacterium tuberculosis
6.1.1.4 2-(4-hydroxy-2-methylanilino)-6-(propan-2-yl)pyrimidin-4(3H)-one residual activity compared to wild-type enzyme is 29% Mycobacterium tuberculosis
6.1.1.4 2-(4-hydroxy-2-methylanilino)-6-methylpyrimidin-4(3H)-one residual activity compared to wild-type enzyme is 61% Mycobacterium tuberculosis
6.1.1.4 2-(4-hydroxy-2-methylanilino)-6-phenylpyrimidin-4(3H)-one residual activity compared to wild-type enzyme is 94% Mycobacterium tuberculosis
6.1.1.4 2-(4-hydroxyanilino)-6-methylpyrimidin-4(3H)-one residual activity compared to wild-type enzyme is 28% Mycobacterium tuberculosis
6.1.1.4 2-(5-chloro-2-hydroxyanilino)-6-propylpyrimidin-4(3H)-one residual activity compared to wild-type enzyme is 86% Mycobacterium tuberculosis
6.1.1.4 3-(2-hydroxy-5-methylanilino)-1,2,4-triazin-5(4H)-one residual activity compared to wild-type enzyme is 70% Mycobacterium tuberculosis
6.1.1.4 3-(2-hydroxy-5-methylanilino)-6-methyl-1,2,4-triazin-5(4H)-one residual activity compared to wild-type enzyme is 44% Mycobacterium tuberculosis
6.1.1.4 3-(2-hydroxy-5-methylanilino)-6-phenyl-1,2,4-triazin-5(4H)-one residual activity compared to wild-type enzyme is 36% Mycobacterium tuberculosis
6.1.1.4 3-(2-hydroxyanilino)-6-methyl-1,2,4-triazin-5(4H)-one residual activity compared to wild-type enzyme is 38% Mycobacterium tuberculosis
6.1.1.4 3-(3-hydroxy-4-methylanilino)-6-methyl-1,2,4-triazin-5(4H)-one residual activity compared to wild-type enzyme is 83% Mycobacterium tuberculosis
6.1.1.4 3-(3-hydroxyanilino)-6-methyl-1,2,4-triazin-5(4H)-one residual activity compared to wild-type enzyme is 40% Mycobacterium tuberculosis
6.1.1.4 3-(3-hydroxyanilino)-6-phenyl-1,2,4-triazin-5(4H)-one residual activity compared to wild-type enzyme is 57% Mycobacterium tuberculosis
6.1.1.4 3-(4-hydroxy-2-methylanilino)-1,2,4-triazin-5(4H)-one residual activity compared to wild-type enzyme is 51% Mycobacterium tuberculosis
6.1.1.4 3-(4-hydroxy-2-methylanilino)-6-methyl-1,2,4-triazin-5(4H)-one residual activity compared to wild-type enzyme is 70% Mycobacterium tuberculosis
6.1.1.4 3-(4-hydroxyanilino)-6-methyl-1,2,4-triazin-5(4H)-one residual activity compared to wild-type enzyme is 55% Mycobacterium tuberculosis
6.1.1.4 3-(4-hydroxyanilino)-6-phenyl-1,2,4-triazin-5(4H)-one residual activity compared to wild-type enzyme is 36% Mycobacterium tuberculosis
6.1.1.4 3-(5-chloro-2-hydroxyanilino)-1,2,4-triazin-5(4H)-one residual activity compared to wild-type enzyme is 45% Mycobacterium tuberculosis
6.1.1.4 3-(5-chloro-2-hydroxyanilino)-6-methyl-1,2,4-triazin-5(4H)-one residual activity compared to wild-type enzyme is 42% Mycobacterium tuberculosis
6.1.1.4 3-[(3-oxo-2,3-dihydro-1,2,4-triazin-5-yl)amino]benzoic acid residual activity compared to wild-type enzyme is 69% Mycobacterium tuberculosis
6.1.1.4 3-[(4-oxo-3,4-dihydroquinazolin-2-yl)amino]benzoic acid residual activity compared to wild-type enzyme is 36% Mycobacterium tuberculosis
6.1.1.4 3-[(6-methyl-3-oxo-2,3-dihydro-1,2,4-triazin-5-yl)amino]benzoic acid residual activity compared to wild-type enzyme is 57% Mycobacterium tuberculosis
6.1.1.4 3-[4-(2-oxopropyl)anilino]-6-phenyl-1,2,4-triazin-5(4H)-one residual activity compared to wild-type enzyme is 52% Mycobacterium tuberculosis
6.1.1.4 4-methyl-3-[(3-oxo-2,3-dihydro-1,2,4-triazin-5-yl)amino]benzoic acid residual activity compared to wild-type enzyme is 65% Mycobacterium tuberculosis
6.1.1.4 4-methyl-3-[(4-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)amino]benzoic acid residual activity compared to wild-type enzyme is 56% Mycobacterium tuberculosis
6.1.1.4 4-[(4-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)amino]benzoic acid residual activity compared to wild-type enzyme is 70% Mycobacterium tuberculosis
6.1.1.4 4-[(5-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)amino]benzoic acid residual activity compared to wild-type enzyme is 71% Mycobacterium tuberculosis
6.1.1.4 4-[(5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)amino]benzoic acid residual activity compared to wild-type enzyme is 70% Mycobacterium tuberculosis
6.1.1.4 4-[(6-methyl-3-oxo-2,3-dihydro-1,2,4-triazin-5-yl)amino]benzoic acid residual activity compared to wild-type enzyme is 64% Mycobacterium tuberculosis
6.1.1.4 5-(2-hydroxy-4-methylanilino)-1,2,4-triazin-3(2H)-one residual activity compared to wild-type enzyme is 73% Mycobacterium tuberculosis
6.1.1.4 5-(2-hydroxy-5-methylanilino)-1,2,4-triazin-3(2H)-one residual activity compared to wild-type enzyme is 70% Mycobacterium tuberculosis
6.1.1.4 5-(2-hydroxyanilino)-1,2,4-triazin-3(2H)-one residual activity compared to wild-type enzyme is 72% Mycobacterium tuberculosis
6.1.1.4 5-(2-hydroxyanilino)-6-methyl-1,2,4-triazin-3(2H)-one residual activity compared to wild-type enzyme is 67% Mycobacterium tuberculosis
6.1.1.4 5-(4-hydroxy-2-methylanilino)-6-methyl-1,2,4-triazin-3(2H)-one residual activity compared to wild-type enzyme is 72% Mycobacterium tuberculosis
6.1.1.4 5-(4-hydroxyanilino)-1,2,4-triazin-3(2H)-one residual activity compared to wild-type enzyme is 70% Mycobacterium tuberculosis
6.1.1.4 5-(4-hydroxyanilino)-6-methyl-1,2,4-triazin-3(2H)-one residual activity compared to wild-type enzyme is 55% Mycobacterium tuberculosis
6.1.1.4 5-(5-chloro-2-hydroxy-phenylamino)-2H-[1,2,4]triazin-3-one binding mode, overview Homo sapiens
6.1.1.4 5-(5-chloro-2-hydroxy-phenylamino)-2H-[1,2,4]triazin-3-one residual activity compared to wild-type enzyme is 18%, binding mode, overview Mycobacterium tuberculosis
6.1.1.4 5-(5-chloro-2-hydroxy-phenylamino)-6-methyl-2H-[1,2,4]triazin-3-one binding mode, overview Homo sapiens
6.1.1.4 5-(5-chloro-2-hydroxy-phenylamino)-6-methyl-2H-[1,2,4]triazin-3-one residual activity compared to wild-type enzyme is 2.3%, binding mode, overview Mycobacterium tuberculosis
6.1.1.4 5-phenylamino-2H-[1,2,4]triazin-3-one
-
 Mycobacterium tuberculosis
6.1.1.4 5-[(6-methyl-3-oxo-2,3-dihydro-1,2,4-triazin-5-yl)amino]benzene-1,3-dicarboxylic acid residual activity compared to wild-type enzyme is 72% Mycobacterium tuberculosis
6.1.1.4 additional information derivatives of 5-phenylamino-2H-[1,2,4]triazin-3-one as leucyl-tRNA synthetase (LeuRS) inhibitors, docking study, overview. The inhibitory activity of some compounds against pathogenic LeuRS is 10fold higher compared to the human enzyme. Hydrogen bond-foming amino acids in active site of LeuRS are Phe97, Tyr99, Glu103, His109, Tyr113, Asp137, Ser631, Gly678, Glu680, His681, Gln714, Ile717, Lys759, and Ile760 Homo sapiens
6.1.1.4 additional information derivatives of 5-phenylamino-2H-[1,2,4]triazin-3-one as leucyl-tRNA synthetase (LeuRS) inhibitors, docking study, overview. The inhibitory activity of some compounds against pathogenic LeuRS is 10fold higher compared to the human enzyme. Hydrogen bond-foming amino acids in active site of LeuRS are Phe97, Tyr99, Glu103, His109, Tyr113, Asp137, Ser631, Gly678, Glu680, His681, Gln714, Ile717, Lys759, and Ile760. No inhibition by 5-[(6-methyl-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)amino]cyclohexa-2,4-diene-1-carboxylic acid, 4-[(4-oxo-3,4,5,6,7,8-hexahydroquinazolin-2-yl)amino]benzoic acid, 2-(2-hydroxyanilino)-5,6,7,8-tetrahydroquinazolin-4(3H)-one, 4-[(6-oxo-4-propyl-1,6-dihydropyrimidin-2-yl)amino]benzoic acid, 2-(4-hydroxyanilino)-6-propylpyrimidin-4(3H)-one, 2-(2-hydroxyanilino)-6-propylpyrimidin-4(3H)-one, 2-(4-hydroxy-2-methylanilino)-6-propylpyrimidin-4(3H)-one, 2-(3-hydroxy-4-methylanilino)-6-propylpyrimidin-4(3H)-one, 3-(2-hydroxyanilino)-1,2,4-triazin-5(4H)-one, 3-(4-hydroxyanilino)-1,2,4-triazin-5(4H)-one, and 2-(2-hydroxyanilino)-3,5,6,7-tetrahydro-4H-cyclopenta[d]pyrimidin-4-one Mycobacterium tuberculosis
6.1.1.4 [4-[(4-oxo-3,4-dihydroquinazolin-2-yl)amino]phenyl]acetic acid residual activity compared to wild-type enzyme is 37% Mycobacterium tuberculosis
6.1.1.4 [4-[(5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)amino]phenyl]acetic acid residual activity compared to wild-type enzyme is 72% Mycobacterium tuberculosis
6.1.1.4 [4-[(6-methyl-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)amino]phenyl]acetic acid residual activity compared to wild-type enzyme is 71% Mycobacterium tuberculosis

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
6.1.1.4 cytoplasm
-
 Homo sapiens 5737
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
6.1.1.4 Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
6.1.1.4 ATP + L-leucine + tRNALeu Homo sapiens
-
 AMP + diphosphate + L-leucyl-tRNALeu
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
6.1.1.4 Homo sapiens Q9P2J5
-
-
6.1.1.4 Mycobacterium tuberculosis P9WFV1
-
-
6.1.1.4 Mycobacterium tuberculosis ATCC 25618 / H37Rv P9WFV1
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
6.1.1.4 recombinant His-tagged enzyme from Escherichia coli strain Rosetta (DE3) by nickel affinity chromatography and dialysis, to homogeneity Homo sapiens
6.1.1.4 recombinant His-tagged enzyme from Escherichia coli strain Rosetta (DE3) by nickel affinity chromatography and dialysis, to homogeneity Mycobacterium tuberculosis

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.1.1.4 ATP + L-leucine + tRNALeu
-
 Homo sapiens AMP + diphosphate + L-leucyl-tRNALeu
-
 ?

Synonyms

EC Number Synonyms Comment Organism
6.1.1.4 LARS
-
 Homo sapiens
6.1.1.4 Leucyl-tRNA synthetase
-
 Homo sapiens
6.1.1.4 Leucyl-tRNA synthetase
-
 Mycobacterium tuberculosis
6.1.1.4 LeuRS
-
 Homo sapiens
6.1.1.4 LeuRS
-
 Mycobacterium tuberculosis
6.1.1.4 leuS
-
 Mycobacterium tuberculosis

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
6.1.1.4 37
-
 assay at Homo sapiens
6.1.1.4 37
-
 assay at Mycobacterium tuberculosis

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
6.1.1.4 8
-
 assay at Homo sapiens
6.1.1.4 8
-
 assay at Mycobacterium tuberculosis

Cofactor

EC Number Cofactor Comment Organism Structure
6.1.1.4 ATP
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
6.1.1.4 additional information enzyme structure homology modeling using the structure of Thermus thermophilus LeuRS, PDB ID 2V0C, as template Mycobacterium tuberculosis