152212 20251017144622.0 doi 10.1021/jacsau.4c01140 sideral 143421 ART-2025-143421 eng Ramírez-Cárdenas, Jonathan STD NMR Epitope Perturbation by Mutation Unveils the Mechanism of YM155 as an Arginine-Glycosyltransferases Inhibitor Effective in Treating Enteropathogenic Diseases 2025 Access copy available to the general public Unrestricted Enteropathogenic 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. info:eu-repo/grantAgreement/ES/AEI/AEI/PID2022-142879NB-I00 info:eu-repo/grantAgreement/ES/DGA/E34-17R info:eu-repo/grantAgreement/ES/DGA/LMP58_18 info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-136362NB-I00 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Taleb, Víctor (orcid)0000-0001-9224-5854 Calvaresi, Valeria Struwe, Weston B. El Qaidi, Samir Zhu, Congrui Hasan, Kamrul Zhang, Yingxin Hardwidge, Philip R. Veloz, Billy Universidad de Zaragoza Muñoz-García, Juan C. Hurtado-Guerrero, Ramón (orcid)0000-0002-3122-9401 Angulo, Jesús 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 5, 3 (2025), 1279-1288 JACS Au 2691-3704 6004503 http://zaguan.unizar.es/record/152212/files/texto_completo.pdf Versión publicada 3231222 http://zaguan.unizar.es/record/152212/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:152212 articulos driver 2025-10-17-14:22:17 ARTICLE