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Literature summary extracted from

  • Hewitt, S.N.; Dranow, D.M.; Horst, B.G.; Abendroth, J.A.; Forte, B.; Hallyburton, I.; Jansen, C.; Baragana, B.; Choi, R.; Rivas, K.L.; Hulverson, M.A.; Dumais, M.; Edwards, T.E.; Lorimer, D.D.; Fairlamb, A.H.; Gray, D.W.; Read, K.D.; Lehane, A.M.; Kirk, K.; Myler, P.J.; Wernimont, A.; Walpole, C.; Stacy, R.; Bar, B.a.r.r.
    Biochemical and Structural characterization of selective allosteric inhibitors of the Plasmodium falciparum drug target, prolyl-tRNA-synthetase (2017), ACS Infect. Dis., 3, 34-44 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
6.1.1.15 expressed in Escherichia coli BL21-(DE3)R3 Rosetta cells Plasmodium falciparum

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
6.1.1.15 sitting drop vapor diffusion method, using 10% (w/v) PEG-800, 20% (v/v) ethylene glycol, 0.1 M MES/imidazole, pH 6.5, and 0.03 M each sodium fluoride, sodium bromide, and sodium iodide Plasmodium falciparum

Inhibitors

EC Number Inhibitors Comment Organism Structure
6.1.1.15 2-[4-(4-fluorophenyl)-5-[[(4-fluorophenyl)carbamoyl]amino]-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetamide
-
 Plasmodium falciparum
6.1.1.15 3-[4-(4-fluorophenyl)-5-[[(4-fluorophenyl)carbamoyl]amino]-1-methyl-1H-pyrazol-3-yl]propanamide
-
 Plasmodium falciparum
6.1.1.15 4-(4-fluorophenyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-amine
-
 Plasmodium falciparum
6.1.1.15 4-(4-fluorophenyl)-5-[[(4-fluorophenyl)carbamoyl]amino]-1-methyl-1H-pyrazole-3-carboxamide
-
 Plasmodium falciparum
6.1.1.15 febrifugine
-
 Plasmodium falciparum
6.1.1.15 glyburide
-
 Plasmodium falciparum
6.1.1.15 halofuginone
-
 Plasmodium falciparum
6.1.1.15 N-(2,4-difluorophenyl)-N'-[4-(4-fluorophenyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
-
 Plasmodium falciparum
6.1.1.15 N-(3-fluorophenyl)-N'-[4-(4-fluorophenyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
-
 Plasmodium falciparum
6.1.1.15 N-(4-fluorophenyl)-N'-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
-
 Plasmodium falciparum
6.1.1.15 N-(4-fluorophenyl)-N'-[1-methyl-3-(trifluoromethyl)-4-[3-(trifluoromethyl)phenyl]-1H-pyrazol-5-yl]urea
-
 Plasmodium falciparum
6.1.1.15 N-(4-fluorophenyl)-N'-[4-(4-fluorophenyl)-1-(2-hydroxyethyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
-
 Plasmodium falciparum
6.1.1.15 N-(4-fluorophenyl)-N'-[4-(4-fluorophenyl)-1-methyl-1H-pyrazol-5-yl]urea
-
 Plasmodium falciparum
6.1.1.15 N-(4-fluorophenyl)-N'-[4-(4-fluorophenyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
-
 Plasmodium falciparum
6.1.1.15 N-(4-fluorophenyl)-N'-[4-(4-fluorophenyl)-1-methyl-3-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-5-yl]urea
-
 Plasmodium falciparum
6.1.1.15 N-(4-fluorophenyl)-N'-[4-(4-fluorophenyl)-3-(2-hydroxyethyl)-1-methyl-1H-pyrazol-5-yl]urea
-
 Plasmodium falciparum
6.1.1.15 N-(4-fluorophenyl)-N'-[4-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
-
 Plasmodium falciparum
6.1.1.15 N-(4-fluorophenyl)-N'-[4-[2-(2-hydroxyethyl)phenyl]-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
-
 Plasmodium falciparum
6.1.1.15 N-(4-fluorophenyl)-N'-[4-[2-(hydroxymethyl)phenyl]-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
-
 Plasmodium falciparum
6.1.1.15 N-(4-fluorophenyl)-N'-[4-[3-(2-hydroxyethyl)phenyl]-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
-
 Plasmodium falciparum
6.1.1.15 N-([3-[5-[[(4-fluorophenyl)carbamoyl]amino]-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]phenyl]methyl)methanesulfonamide
-
 Plasmodium falciparum
6.1.1.15 N-Boc-halofuginone less than 20% inhibition at 1 mM Plasmodium falciparum
6.1.1.15 N-[3-(2-cyanoethyl)-4-(4-fluorophenyl)-1-methyl-1H-pyrazol-5-yl]-N'-(4-fluorophenyl)urea
-
 Plasmodium falciparum
6.1.1.15 N-[3-(cyanomethyl)-4-(4-fluorophenyl)-1-methyl-1H-pyrazol-5-yl]-N'-(4-fluorophenyl)urea
-
 Plasmodium falciparum
6.1.1.15 N-[3-cyano-4-(4-fluorophenyl)-1-methyl-1H-pyrazol-5-yl]-N'-(4-fluorophenyl)urea
-
 Plasmodium falciparum
6.1.1.15 N-[3-[2-(dimethylamino)ethyl]-4-(4-fluorophenyl)-1-methyl-1H-pyrazol-5-yl]-N'-(4-fluorophenyl)urea
-
 Plasmodium falciparum
6.1.1.15 N-[4-(3,4-difluorophenyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]-N'-(4-fluorophenyl)urea
-
 Plasmodium falciparum
6.1.1.15 N-[4-(4-fluorophenyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]-N'-(4-methoxyphenyl)urea
-
 Plasmodium falciparum
6.1.1.15 N-[4-(4-fluorophenyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]-N'-[2-(morpholin-4-yl)pyridin-4-yl]urea
-
 Plasmodium falciparum
6.1.1.15 N-[4-bromo-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]-N'-(4-fluorophenyl)urea
-
 Plasmodium falciparum
6.1.1.15 TCMDC-124506 competitive inhibitor Plasmodium falciparum

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
6.1.1.15 ATP + L-proline + tRNAPro Plasmodium falciparum
-
 AMP + diphosphate + L-prolyl-tRNAPro
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
6.1.1.15 Plasmodium falciparum Q8I5R7
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
6.1.1.15 His Trap column chromatography and Superdex 75 gel filtration Plasmodium falciparum

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.1.1.15 ATP + L-proline + tRNAPro
-
 Plasmodium falciparum AMP + diphosphate + L-prolyl-tRNAPro
-
 ?

Synonyms

EC Number Synonyms Comment Organism
6.1.1.15 Prolyl-tRNA synthetase
-
 Plasmodium falciparum
6.1.1.15 ProRS
-
 Plasmodium falciparum

Cofactor

EC Number Cofactor Comment Organism Structure
6.1.1.15 ATP
-
 Plasmodium falciparum

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
6.1.1.15 0.0025
-
 at pH 7.0 and 37°C Plasmodium falciparum N-(2,4-difluorophenyl)-N'-[4-(4-fluorophenyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
6.1.1.15 0.003
-
 at pH 7.0 and 37°C Plasmodium falciparum N-(4-fluorophenyl)-N'-[4-(4-fluorophenyl)-1-methyl-3-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-5-yl]urea
6.1.1.15 0.004
-
 at pH 7.0 and 37°C Plasmodium falciparum N-[3-[2-(dimethylamino)ethyl]-4-(4-fluorophenyl)-1-methyl-1H-pyrazol-5-yl]-N'-(4-fluorophenyl)urea
6.1.1.15 0.005
-
 at pH 7.0 and 37°C Plasmodium falciparum N-(4-fluorophenyl)-N'-[4-(4-fluorophenyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
6.1.1.15 0.005
-
 at pH 7.0 and 37°C Plasmodium falciparum N-[3-cyano-4-(4-fluorophenyl)-1-methyl-1H-pyrazol-5-yl]-N'-(4-fluorophenyl)urea
6.1.1.15 0.005
-
 at pH 7.0 and 37°C Plasmodium falciparum TCMDC-124506
6.1.1.15 0.006
-
 at pH 7.0 and 37°C Plasmodium falciparum N-[3-(cyanomethyl)-4-(4-fluorophenyl)-1-methyl-1H-pyrazol-5-yl]-N'-(4-fluorophenyl)urea
6.1.1.15 0.008
-
 at pH 7.0 and 37°C Plasmodium falciparum N-(3-fluorophenyl)-N'-[4-(4-fluorophenyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
6.1.1.15 0.008
-
 at pH 7.0 and 37°C Plasmodium falciparum 3-[4-(4-fluorophenyl)-5-[[(4-fluorophenyl)carbamoyl]amino]-1-methyl-1H-pyrazol-3-yl]propanamide
6.1.1.15 0.009
-
 at pH 7.0 and 37°C Plasmodium falciparum N-[3-(2-cyanoethyl)-4-(4-fluorophenyl)-1-methyl-1H-pyrazol-5-yl]-N'-(4-fluorophenyl)urea
6.1.1.15 0.013
-
 at pH 7.0 and 37°C Plasmodium falciparum N-(4-fluorophenyl)-N'-[4-[3-(2-hydroxyethyl)phenyl]-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
6.1.1.15 0.014
-
 at pH 7.0 and 37°C Plasmodium falciparum 4-(4-fluorophenyl)-5-[[(4-fluorophenyl)carbamoyl]amino]-1-methyl-1H-pyrazole-3-carboxamide
6.1.1.15 0.018
-
 at pH 7.0 and 37°C Plasmodium falciparum N-(4-fluorophenyl)-N'-[4-(4-fluorophenyl)-3-(2-hydroxyethyl)-1-methyl-1H-pyrazol-5-yl]urea
6.1.1.15 0.02
-
 at pH 7.0 and 37°C Plasmodium falciparum N-(4-fluorophenyl)-N'-[4-[2-(hydroxymethyl)phenyl]-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
6.1.1.15 0.05
-
 IC50 above 0.05 mM, at pH 7.0 and 37°C Plasmodium falciparum 4-(4-fluorophenyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-amine
6.1.1.15 0.05
-
 IC50 above 0.05 mM, at pH 7.0 and 37°C Plasmodium falciparum N-(4-fluorophenyl)-N'-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
6.1.1.15 0.05
-
 IC50 above 0.05 mM, at pH 7.0 and 37°C Plasmodium falciparum N-(4-fluorophenyl)-N'-[4-(4-fluorophenyl)-1-(2-hydroxyethyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
6.1.1.15 0.05
-
 IC50 above 0.05 mM, at pH 7.0 and 37°C Plasmodium falciparum N-(4-fluorophenyl)-N'-[4-(4-fluorophenyl)-1-methyl-1H-pyrazol-5-yl]urea
6.1.1.15 0.05
-
 IC50 above 0.05 mM, at pH 7.0 and 37°C Plasmodium falciparum N-(4-fluorophenyl)-N'-[4-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
6.1.1.15 0.05
-
 IC50 above 0.05 mM, at pH 7.0 and 37°C Plasmodium falciparum N-[4-(3,4-difluorophenyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]-N'-(4-fluorophenyl)urea
6.1.1.15 0.05
-
 IC50 above 0.05 mM, at pH 7.0 and 37°C Plasmodium falciparum N-[4-(4-fluorophenyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]-N'-(4-methoxyphenyl)urea
6.1.1.15 0.05
-
 IC50 above 0.05 mM, at pH 7.0 and 37°C Plasmodium falciparum N-[4-(4-fluorophenyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]-N'-[2-(morpholin-4-yl)pyridin-4-yl]urea
6.1.1.15 0.05
-
 IC50 above 0.05 mM, at pH 7.0 and 37°C Plasmodium falciparum N-[4-bromo-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]-N'-(4-fluorophenyl)urea
6.1.1.15 0.05
-
 IC50 above 0.05 mM, at pH 7.0 and 37°C Plasmodium falciparum 2-[4-(4-fluorophenyl)-5-[[(4-fluorophenyl)carbamoyl]amino]-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetamide
6.1.1.15 0.05
-
 IC50 above 0.05 mM, at pH 7.0 and 37°C Plasmodium falciparum N-(4-fluorophenyl)-N'-[4-[2-(2-hydroxyethyl)phenyl]-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea
6.1.1.15 0.05
-
 IC50 above 0.05 mM, at pH 7.0 and 37°C Plasmodium falciparum N-([3-[5-[[(4-fluorophenyl)carbamoyl]amino]-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]phenyl]methyl)methanesulfonamide
6.1.1.15 0.05
-
 IC50 above 0.05 mM, at pH 7.0 and 37°C Plasmodium falciparum N-(4-fluorophenyl)-N'-[1-methyl-3-(trifluoromethyl)-4-[3-(trifluoromethyl)phenyl]-1H-pyrazol-5-yl]urea