000151147 001__ 151147
000151147 005__ 20251017144607.0
000151147 0247_ $$2doi$$a10.1039/d1sc04065k
000151147 0248_ $$2sideral$$a125795
000151147 037__ $$aART-2021-125795
000151147 041__ $$aeng
000151147 100__ $$0(orcid)0000-0003-3791-2997$$aGarcía-García A.$$uUniversidad de Zaragoza
000151147 245__ $$aNleB/SseK-catalyzed arginine-glycosylation and enteropathogen virulence are finely tuned by a single variable position contiguous to the catalytic machinery
000151147 260__ $$c2021
000151147 5060_ $$aAccess copy available to the general public$$fUnrestricted
000151147 5203_ $$aNleB/SseK effectors are arginine-GlcNAc-transferases expressed by enteric bacterial pathogens that modify host cell proteins to disrupt signaling pathways. While the conservedCitrobacter rodentiumNleB andE. coliNleB1 proteins display a broad selectivity towards host proteins, Salmonella entericaSseK1, SseK2, and SseK3 have a narrowed protein substrate selectivity. Here, by combining computational and biophysical experiments, we demonstrate that the broad protein substrate selectivity of NleB relies on Tyr284NleB/NleB1, a second-shell residue contiguous to the catalytic machinery. Tyr284NleB/NleB1is important in coupling protein substrate binding to catalysis. This is exemplified by S286YSseK1and N302YSseK2mutants, which become active towards FADD and DR3 death domains, respectively, and whose kinetic properties match those of enterohemorrhagicE. coliNleB1. The integration of these mutants intoS. entericaincreasesS. entericasurvival in macrophages, suggesting that better enzymatic kinetic parameters lead to enhanced virulence. Our findings provide insights into how these enzymes finely tune arginine-glycosylation and, in turn, bacterial virulence. In addition, our data show how promiscuous glycosyltransferases preferentially glycosylate specific protein substrates.
000151147 536__ $$9info:eu-repo/grantAgreement/ES/DGA-FEDER/E34-R17$$9info:eu-repo/grantAgreement/ES/DGA/LMP58-18$$9info:eu-repo/grantAgreement/ES/MICINN/BFU2016-75633-P$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-105451GB-I00
000151147 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttps://creativecommons.org/licenses/by-nc/4.0/deed.es
000151147 590__ $$a9.969$$b2021
000151147 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b25 / 179 = 0.14$$c2021$$dQ1$$eT1
000151147 592__ $$a2.878$$b2021
000151147 593__ $$aChemistry (miscellaneous)$$c2021$$dQ1
000151147 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000151147 700__ $$aHicks T.
000151147 700__ $$aEl Qaidi S.
000151147 700__ $$aZhu C.
000151147 700__ $$aHardwidge P.R.
000151147 700__ $$aAngulo J.
000151147 700__ $$0(orcid)0000-0002-3122-9401$$aHurtado-Guerrero R.
000151147 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000151147 773__ $$g12, 36 (2021), 12181-12191$$pChem. sci.$$tCHEMICAL SCIENCE$$x2041-6520
000151147 8564_ $$s1530777$$uhttps://zaguan.unizar.es/record/151147/files/texto_completo.pdf$$yVersión publicada
000151147 8564_ $$s2851755$$uhttps://zaguan.unizar.es/record/151147/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000151147 909CO $$ooai:zaguan.unizar.es:151147$$particulos$$pdriver
000151147 951__ $$a2025-10-17-14:15:54
000151147 980__ $$aARTICLE