Ramírez Cárdenas, JonathanTaleb, VíctorCalvaresi, ValeriaStruwe, WBEl Qaidi, SamirZhu, CongruiMuñoz García, Juan CarlosAngulo Álvarez, Jesús2025-06-062025-06-062025-03Ramírez Cárdenas, J., Taleb, V., Calvaresi, V., Struwe, W., El Qaidi, S., Zhu, C.,...,Angulo Álvarez, J. (2025). STD NMR Epitope Perturbation by Mutation Unveils the Mechanismof YM155 as an Arginine-Glycosyltransferases Inhibitor Effective inTreating Enteropathogenic Diseases. Jacs Au, 5 (3), 1279-1288. https://doi.org/10.1021/jacsau.4c01140?urlappend=%3Fref%3DPDF&jav=VoR&rel=cite-as.2691-3704https://hdl.handle.net/11441/174045Enteropathogenic arginine-glycosyltransferases(Arg-GTs) alter higher eukaryotic proteins by attaching a GlcNAcresidue to arginine acceptor sites, disrupting essential pathwayssuch as NF-κB signaling, which promotes bacterial survival. Theseenzymes are potential drug targets for treating related diseases. Inthis study, we present a novel STD NMR Epitope Perturbation byMutation spectroscopic approach that, in combination withhydrogen−deuterium exchange mass spectrometry (HDX-MS),and molecular dynamics simulations, shows that the highly potentbroad-spectrum anticancer drug YM155 serves as a potentialnoncompetitive inhibitor of these enzymes. It induces aconformation of the arginine acceptor site unfavorable for GlcNActransfer, which underlies the molecular mechanism by which thiscompound exerts its inhibitory function. Finally, we also demonstrate that YM155 effectively treats enteropathogenic diseases in amouse model, highlighting its therapeutic potential. Overall, our data suggest that this compound can be repurposed to not only treatcancer but also infectious diseases.application/pdf10 p.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Enteropathogenic arginine-glycosyltransferasesArginine N-glycosyltransferase inhibitionSTD NMR epitope perturbation by mutationEnzyme inhibitorsinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccesshttps://doi.org/10.1021/jacsau.4c01140?urlappend=%3Fref%3DPDF&jav=VoR&rel=cite-as