Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase
Xie S, Wang Y, Morton C, Metcalfe R, Dogovski C, Pasaje C, Dunn E, Luth M, Kumpornsin K, Istvan E, Park J, Fairhurst K, Ketprasit N, Yeo T, Yildirim O, Bhebhe M, Klug D, Rutledge P, Godoy L, Dey S, De Souza M, Siqueira-Neto J, Du Y, Puhalovich T, Amini M, Shami G, Loesbanluechai D, Nie S, Williamson N, Jana G, Maity B, Thomson P, Foley T, Tan D, Niles J, Han B, Goldberg D, Burrows J, Fidock D, Lee M, Winzeler E, Griffin M, Todd M, Tilley L. Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase. Nature Communications 2024, 15: 937. PMID: 38297033, PMCID: PMC10831071, DOI: 10.1038/s41467-024-45224-z.Peer-Reviewed Original ResearchConceptsX-ray crystallographic studiesStructure-activity relationshipSynthetically accessible scaffoldMass spectrometryTargeted mass spectrometryAccessible scaffoldInhibitor adductX-rayMechanism of actionAmino acid starvation responseMammalian cell toxicityPro inhibitorsAdductsLow mammalian cell toxicityParasite culturesDeploying drugsInhibitor classCell toxicityReactionPlasmodiumResistance developmentLow propensityIncreased resistanceInhibitionSpectrometry
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