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Literature summary extracted from

  • Shibata, S.; Gillespie, J.R.; Kelley, A.M.; Napuli, A.J.; Zhang, Z.; Kovzun, K.V.; Pefley, R.M.; Lam, J.; Zucker, F.H.; Van Voorhis, W.C.; Merritt, E.A.; Hol, W.G.; Verlinde, C.L.; Fan, E.; Buckner, F.S.
    Selective inhibitors of methionyl-tRNA synthetase have potent activity against Trypanosoma brucei infection in mice (2011), Antimicrob. Agents Chemother., 55, 1982-1989.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
6.1.1.10 drug development parasite MetRS is an attractive drug target due to its essential role in protein synthesis and cell survival. Comparative sequence analysis discloses differences between the trypanosome and mammalian methionyl-tRNA synthetases Trypanosoma brucei

Inhibitors

EC Number Inhibitors Comment Organism Structure
6.1.1.10 2-([3-[(2,3-dichlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 77.9% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-([3-[(2,4-dichlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 87.1% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-([3-[(2,5-dichlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 93.1% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-([3-[(2,6-dichlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 51.3% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-([3-[(2-chlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 31.8% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-([3-[(3,4-dichlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 91.7% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-([3-[(3,5-dibromo-2-ethoxybenzyl)amino]propyl]amino)quinolin-4(1H)-one 98.2% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-([3-[(3,5-dibromo-2-methoxybenzyl)amino]propyl]amino)quinolin-4(1H)-one 95.0% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-([3-[(3,5-dibromobenzyl)amino]propyl]amino)quinolin-4(1H)-one 98.8% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-([3-[(3,5-dichlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 99.2% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-([3-[(3,5-difluorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 45.8% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-([3-[(3,5-dimethoxybenzyl)amino]propyl]amino)quinolin-4(1H)-one 35.3% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-([3-[(3,5-dimethylbenzyl)amino]propyl]amino)quinolin-4(1H)-one 91.1% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-([3-[(3-bromobenzyl)amino]propyl]amino)quinolin-4(1H)-one 82.7% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-([3-[(3-chlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 97.3% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-([3-[(3-ethoxybenzyl)amino]propyl]amino)quinolin-4(1H)-one 19.1% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-([3-[(4-chlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 52.0% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-[(3-[[3,5-bis(trifluoromethyl)benzyl]amino]propyl)amino]quinolin-4(1H)-one 36.9% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-[(3-[[3-(trifluoromethoxy)benzyl]amino]propyl)amino]quinolin-4(1H)-one 56.5% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 2-[[3-(benzylamino)propyl]amino]quinolin-4(1H)-one 9.0% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 3-[([3-[(4-oxo-1,4-dihydroquinolin-2-yl)amino]propyl]amino)methyl]benzonitrile 20.2% inhibition at 50 nM Trypanosoma brucei
6.1.1.10 additional information a homology model of the Trypanosoma brucei MetRS based on other MetRS structures is used to model binding of lead diaryl diamine compounds in the design and development of selective parasite MetRS inhibitors for treatment of African trypanosomiasis, overview Trypanosoma brucei

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
6.1.1.10 Mg2+ required Trypanosoma brucei

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
6.1.1.10 ATP + L-methionine + tRNAMet Trypanosoma brucei
-
AMP + diphosphate + L-methionyl-tRNAMet
-
?

Organism

EC Number Organism UniProt Comment Textmining
6.1.1.10 Trypanosoma brucei
-
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.1.1.10 ATP + L-methionine + tRNAMet
-
Trypanosoma brucei AMP + diphosphate + L-methionyl-tRNAMet
-
?

Subunits

EC Number Subunits Comment Organism
6.1.1.10 More homology modeling and ligand docking studies of trypanosomatid MetRS enzymes, structure comparisons, overview Trypanosoma brucei

Synonyms

EC Number Synonyms Comment Organism
6.1.1.10 methionyl-tRNA synthetase
-
Trypanosoma brucei
6.1.1.10 MetRS
-
Trypanosoma brucei

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
6.1.1.10 22
-
assay at room temperature Trypanosoma brucei

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
6.1.1.10 7.9
-
assay at Trypanosoma brucei

Cofactor

EC Number Cofactor Comment Organism Structure
6.1.1.10 ATP
-
Trypanosoma brucei

General Information

EC Number General Information Comment Organism
6.1.1.10 metabolism the single MetRS of Trypanosoma brucei is essential for normal cell growth Trypanosoma brucei