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