000152212 001__ 152212 000152212 005__ 20250401114419.0 000152212 0247_ $$2doi$$a10.1021/jacsau.4c01140 000152212 0248_ $$2sideral$$a143421 000152212 037__ $$aART-2025-143421 000152212 041__ $$aeng 000152212 100__ $$aRamírez-Cárdenas, Jonathan 000152212 245__ $$aSTD NMR Epitope Perturbation by Mutation Unveils the Mechanism of YM155 as an Arginine-Glycosyltransferases Inhibitor Effective in Treating Enteropathogenic Diseases 000152212 260__ $$c2025 000152212 5060_ $$aAccess copy available to the general public$$fUnrestricted 000152212 5203_ $$aEnteropathogenic arginine-glycosyltransferases (Arg-GTs) alter higher eukaryotic proteins by attaching a GlcNAc residue to arginine acceptor sites, disrupting essential pathways such as NF-κB signaling, which promotes bacterial survival. These enzymes are potential drug targets for treating related diseases. In this study, we present a novel STD NMR Epitope Perturbation by Mutation spectroscopic approach that, in combination with hydrogen–deuterium exchange mass spectrometry (HDX-MS), and molecular dynamics simulations, shows that the highly potent broad-spectrum anticancer drug YM155 serves as a potential noncompetitive inhibitor of these enzymes. It induces a conformation of the arginine acceptor site unfavorable for GlcNAc transfer, which underlies the molecular mechanism by which this compound exerts its inhibitory function. Finally, we also demonstrate that YM155 effectively treats enteropathogenic diseases in a mouse model, highlighting its therapeutic potential. Overall, our data suggest that this compound can be repurposed to not only treat cancer but also infectious diseases. 000152212 536__ $$9info:eu-repo/grantAgreement/ES/AEI/AEI/PID2022-142879NB-I00$$9info:eu-repo/grantAgreement/ES/DGA/E34-17R$$9info:eu-repo/grantAgreement/ES/DGA/LMP58_18$$9info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-136362NB-I00 000152212 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000152212 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000152212 700__ $$0(orcid)0000-0001-9224-5854$$aTaleb, Víctor 000152212 700__ $$aCalvaresi, Valeria 000152212 700__ $$aStruwe, Weston B. 000152212 700__ $$aEl Qaidi, Samir 000152212 700__ $$aZhu, Congrui 000152212 700__ $$aHasan, Kamrul 000152212 700__ $$aZhang, Yingxin 000152212 700__ $$aHardwidge, Philip R. 000152212 700__ $$aVeloz, Billy$$uUniversidad de Zaragoza 000152212 700__ $$aMuñoz-García, Juan C. 000152212 700__ $$0(orcid)0000-0002-3122-9401$$aHurtado-Guerrero, Ramón 000152212 700__ $$aAngulo, Jesús 000152212 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole. 000152212 773__ $$g5, 3 (2025), 1279-1288$$tJACS Au$$x2691-3704 000152212 8564_ $$s6004503$$uhttps://zaguan.unizar.es/record/152212/files/texto_completo.pdf$$yVersión publicada 000152212 8564_ $$s3231222$$uhttps://zaguan.unizar.es/record/152212/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000152212 909CO $$ooai:zaguan.unizar.es:152212$$particulos$$pdriver 000152212 951__ $$a2025-04-01-11:02:53 000152212 980__ $$aARTICLE