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Literature summary for 6.1.1.10 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
Search for more literature for 6.1.1.10

Application

Application Comment Organism
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

Inhibitors Comment Organism Structure
2-([3-[(2,3-dichlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 77.9% inhibition at 50 nM Trypanosoma brucei
2-([3-[(2,4-dichlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 87.1% inhibition at 50 nM Trypanosoma brucei
2-([3-[(2,5-dichlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 93.1% inhibition at 50 nM Trypanosoma brucei
2-([3-[(2,6-dichlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 51.3% inhibition at 50 nM Trypanosoma brucei
2-([3-[(2-chlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 31.8% inhibition at 50 nM Trypanosoma brucei
2-([3-[(3,4-dichlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 91.7% inhibition at 50 nM Trypanosoma brucei
2-([3-[(3,5-dibromo-2-ethoxybenzyl)amino]propyl]amino)quinolin-4(1H)-one 98.2% inhibition at 50 nM Trypanosoma brucei
2-([3-[(3,5-dibromo-2-methoxybenzyl)amino]propyl]amino)quinolin-4(1H)-one 95.0% inhibition at 50 nM Trypanosoma brucei
2-([3-[(3,5-dibromobenzyl)amino]propyl]amino)quinolin-4(1H)-one 98.8% inhibition at 50 nM Trypanosoma brucei
2-([3-[(3,5-dichlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 99.2% inhibition at 50 nM Trypanosoma brucei
2-([3-[(3,5-difluorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 45.8% inhibition at 50 nM Trypanosoma brucei
2-([3-[(3,5-dimethoxybenzyl)amino]propyl]amino)quinolin-4(1H)-one 35.3% inhibition at 50 nM Trypanosoma brucei
2-([3-[(3,5-dimethylbenzyl)amino]propyl]amino)quinolin-4(1H)-one 91.1% inhibition at 50 nM Trypanosoma brucei
2-([3-[(3-bromobenzyl)amino]propyl]amino)quinolin-4(1H)-one 82.7% inhibition at 50 nM Trypanosoma brucei
2-([3-[(3-chlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 97.3% inhibition at 50 nM Trypanosoma brucei
2-([3-[(3-ethoxybenzyl)amino]propyl]amino)quinolin-4(1H)-one 19.1% inhibition at 50 nM Trypanosoma brucei
2-([3-[(4-chlorobenzyl)amino]propyl]amino)quinolin-4(1H)-one 52.0% inhibition at 50 nM Trypanosoma brucei
2-[(3-[[3,5-bis(trifluoromethyl)benzyl]amino]propyl)amino]quinolin-4(1H)-one 36.9% inhibition at 50 nM Trypanosoma brucei
2-[(3-[[3-(trifluoromethoxy)benzyl]amino]propyl)amino]quinolin-4(1H)-one 56.5% inhibition at 50 nM Trypanosoma brucei
2-[[3-(benzylamino)propyl]amino]quinolin-4(1H)-one 9.0% inhibition at 50 nM Trypanosoma brucei
3-[([3-[(4-oxo-1,4-dihydroquinolin-2-yl)amino]propyl]amino)methyl]benzonitrile 20.2% inhibition at 50 nM Trypanosoma brucei
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

Metals/Ions Comment Organism Structure
Mg2+ required Trypanosoma brucei

Natural Substrates/ Products (Substrates)

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

Organism

Organism UniProt Comment Textmining
Trypanosoma brucei
-
-
-

Substrates and Products (Substrate)

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

Subunits

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

Synonyms

Synonyms Comment Organism
methionyl-tRNA synthetase
-
 Trypanosoma brucei
MetRS
-
 Trypanosoma brucei

Temperature Optimum [°C]

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

pH Optimum

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

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Trypanosoma brucei

General Information

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