Application | Comment | Organism |
---|---|---|
drug development | leucyl-tRNA synthetase (LeuRS) is an attractive therapeutic target and a target for development of drugs | Mycobacterium tuberculosis |
Cloned (Comment) | Organism |
---|---|
gene LARS, recombinant expression of C-terminally His-tagged enzyme in Escherichia coli strain Rosetta (DE3) | Homo sapiens |
gene leuS, recombinant expression of His-tagged enzyme in Escherichia coli strain Rosetta (DE3) | Mycobacterium tuberculosis |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
2-(2,5-dimethylanilino)-5,6,7,8-tetrahydroquinazolin-4(3H)-one | residual activity compared to wild-type enzyme is 71% | Mycobacterium tuberculosis | |
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 | |
2-(2-hydroxy-5-methylanilino)-6-propylpyrimidin-4(3H)-one | residual activity compared to wild-type enzyme is 93% | Mycobacterium tuberculosis | |
2-(2-hydroxy-5-methylanilino)quinazolin-4(3H)-one | residual activity compared to wild-type enzyme is 26% | Mycobacterium tuberculosis | |
2-(2-hydroxyanilino)-6-methylpyrimidin-4(3H)-one | residual activity compared to wild-type enzyme is 42% | Mycobacterium tuberculosis | |
2-(2-hydroxyanilino)pyrimidin-4(3H)-one | residual activity compared to wild-type enzyme is 37% | Mycobacterium tuberculosis | |
2-(2-hydroxyanilino)quinazolin-4(3H)-one | residual activity compared to wild-type enzyme is 36% | Mycobacterium tuberculosis | |
2-(3-hydroxy-4-methylanilino)-6-propylpyrimidin-4(3H)-one | residual activity compared to wild-type enzyme is 36% | Mycobacterium tuberculosis | |
2-(3-hydroxyanilino)-6-methylpyrimidin-4(3H)-one | residual activity compared to wild-type enzyme is 39% | Mycobacterium tuberculosis | |
2-(3-hydroxyanilino)quinazolin-4(3H)-one | residual activity compared to wild-type enzyme is 26% | Mycobacterium tuberculosis | |
2-(4-hydroxy-2-methylanilino)-5,6,7,8-tetrahydroquinazolin-4(3H)-one | residual activity compared to wild-type enzyme is 70% | Mycobacterium tuberculosis | |
2-(4-hydroxy-2-methylanilino)-6-(propan-2-yl)pyrimidin-4(3H)-one | residual activity compared to wild-type enzyme is 29% | Mycobacterium tuberculosis | |
2-(4-hydroxy-2-methylanilino)-6-methylpyrimidin-4(3H)-one | residual activity compared to wild-type enzyme is 61% | Mycobacterium tuberculosis | |
2-(4-hydroxy-2-methylanilino)-6-phenylpyrimidin-4(3H)-one | residual activity compared to wild-type enzyme is 94% | Mycobacterium tuberculosis | |
2-(4-hydroxyanilino)-6-methylpyrimidin-4(3H)-one | residual activity compared to wild-type enzyme is 28% | Mycobacterium tuberculosis | |
2-(5-chloro-2-hydroxyanilino)-6-propylpyrimidin-4(3H)-one | residual activity compared to wild-type enzyme is 86% | Mycobacterium tuberculosis | |
3-(2-hydroxy-5-methylanilino)-1,2,4-triazin-5(4H)-one | residual activity compared to wild-type enzyme is 70% | Mycobacterium tuberculosis | |
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 | |
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 | |
3-(2-hydroxyanilino)-6-methyl-1,2,4-triazin-5(4H)-one | residual activity compared to wild-type enzyme is 38% | Mycobacterium tuberculosis | |
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 | |
3-(3-hydroxyanilino)-6-methyl-1,2,4-triazin-5(4H)-one | residual activity compared to wild-type enzyme is 40% | Mycobacterium tuberculosis | |
3-(3-hydroxyanilino)-6-phenyl-1,2,4-triazin-5(4H)-one | residual activity compared to wild-type enzyme is 57% | Mycobacterium tuberculosis | |
3-(4-hydroxy-2-methylanilino)-1,2,4-triazin-5(4H)-one | residual activity compared to wild-type enzyme is 51% | Mycobacterium tuberculosis | |
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 | |
3-(4-hydroxyanilino)-6-methyl-1,2,4-triazin-5(4H)-one | residual activity compared to wild-type enzyme is 55% | Mycobacterium tuberculosis | |
3-(4-hydroxyanilino)-6-phenyl-1,2,4-triazin-5(4H)-one | residual activity compared to wild-type enzyme is 36% | Mycobacterium tuberculosis | |
3-(5-chloro-2-hydroxyanilino)-1,2,4-triazin-5(4H)-one | residual activity compared to wild-type enzyme is 45% | Mycobacterium tuberculosis | |
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 | |
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 | |
3-[(4-oxo-3,4-dihydroquinazolin-2-yl)amino]benzoic acid | residual activity compared to wild-type enzyme is 36% | Mycobacterium tuberculosis | |
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 | |
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 | |
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 | |
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 | |
4-[(4-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)amino]benzoic acid | residual activity compared to wild-type enzyme is 70% | Mycobacterium tuberculosis | |
4-[(5-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)amino]benzoic acid | residual activity compared to wild-type enzyme is 71% | Mycobacterium tuberculosis | |
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 | |
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 | |
5-(2-hydroxy-4-methylanilino)-1,2,4-triazin-3(2H)-one | residual activity compared to wild-type enzyme is 73% | Mycobacterium tuberculosis | |
5-(2-hydroxy-5-methylanilino)-1,2,4-triazin-3(2H)-one | residual activity compared to wild-type enzyme is 70% | Mycobacterium tuberculosis | |
5-(2-hydroxyanilino)-1,2,4-triazin-3(2H)-one | residual activity compared to wild-type enzyme is 72% | Mycobacterium tuberculosis | |
5-(2-hydroxyanilino)-6-methyl-1,2,4-triazin-3(2H)-one | residual activity compared to wild-type enzyme is 67% | Mycobacterium tuberculosis | |
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 | |
5-(4-hydroxyanilino)-1,2,4-triazin-3(2H)-one | residual activity compared to wild-type enzyme is 70% | Mycobacterium tuberculosis | |
5-(4-hydroxyanilino)-6-methyl-1,2,4-triazin-3(2H)-one | residual activity compared to wild-type enzyme is 55% | Mycobacterium tuberculosis | |
5-(5-chloro-2-hydroxy-phenylamino)-2H-[1,2,4]triazin-3-one | binding mode, overview | Homo sapiens | |
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 | |
5-(5-chloro-2-hydroxy-phenylamino)-6-methyl-2H-[1,2,4]triazin-3-one | binding mode, overview | Homo sapiens | |
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 | |
5-phenylamino-2H-[1,2,4]triazin-3-one | - |
Mycobacterium tuberculosis | |
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 | |
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 | |
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 | |
[4-[(4-oxo-3,4-dihydroquinazolin-2-yl)amino]phenyl]acetic acid | residual activity compared to wild-type enzyme is 37% | Mycobacterium tuberculosis | |
[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 | |
[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 | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytoplasm | - |
Homo sapiens | 5737 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + L-leucine + tRNALeu | Homo sapiens | - |
AMP + diphosphate + L-leucyl-tRNALeu | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q9P2J5 | - |
- |
Mycobacterium tuberculosis | P9WFV1 | - |
- |
Mycobacterium tuberculosis ATCC 25618 / H37Rv | P9WFV1 | - |
- |
Purification (Comment) | Organism |
---|---|
recombinant His-tagged enzyme from Escherichia coli strain Rosetta (DE3) by nickel affinity chromatography and dialysis, to homogeneity | Homo sapiens |
recombinant His-tagged enzyme from Escherichia coli strain Rosetta (DE3) by nickel affinity chromatography and dialysis, to homogeneity | Mycobacterium tuberculosis |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + L-leucine + tRNALeu | - |
Homo sapiens | AMP + diphosphate + L-leucyl-tRNALeu | - |
? |
Synonyms | Comment | Organism |
---|---|---|
LARS | - |
Homo sapiens |
Leucyl-tRNA synthetase | - |
Homo sapiens |
Leucyl-tRNA synthetase | - |
Mycobacterium tuberculosis |
LeuRS | - |
Homo sapiens |
LeuRS | - |
Mycobacterium tuberculosis |
leuS | - |
Mycobacterium tuberculosis |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Homo sapiens |
37 | - |
assay at | Mycobacterium tuberculosis |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
8 | - |
assay at | Homo sapiens |
8 | - |
assay at | Mycobacterium tuberculosis |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
additional information | enzyme structure homology modeling using the structure of Thermus thermophilus LeuRS, PDB ID 2V0C, as template | Mycobacterium tuberculosis |