000063287 001__ 63287
000063287 005__ 20171129112116.0
000063287 0247_ $$2doi$$a10.1038/ncomms2421
000063287 0248_ $$2sideral$$a84077
000063287 037__ $$aART-2013-84077
000063287 041__ $$aeng
000063287 100__ $$aChopra, S.
000063287 245__ $$aPlant tumour biocontrol agent employs a tRNA-dependent mechanism to inhibit leucyl-tRNA synthetase
000063287 260__ $$c2013
000063287 5060_ $$aAccess copy available to the general public$$fUnrestricted
000063287 5203_ $$aLeucyl-tRNA synthetases (LeuRSs) have an essential role in translation and are promising targets for antibiotic development. Agrocin 84 is a LeuRS inhibitor produced by the biocontrol agent Agrobacterium radiobacter K84 that targets pathogenic strains of A. tumefaciens, the causative agent of plant tumours. Agrocin 84 acts as a molecular Trojan horse and is processed inside the pathogen into a toxic moiety (TM84). Here we show using crystal structure, thermodynamic and kinetic analyses, that this natural antibiotic employs a unique and previously undescribed mechanism to inhibit LeuRS. TM84 requires tRNALeu for tight binding to the LeuRS synthetic active site, unlike any previously reported inhibitors. TM84 traps the enzyme–tRNA complex in a novel ‘aminoacylation-like’ conformation, forming novel interactions with the KMSKS loop and the tRNA 30-end. Our findings reveal an intriguing tRNAdependent inhibition mechanism that may confer a distinct evolutionary advantage in vivo and inform future rational antibiotic design.
000063287 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000063287 590__ $$a10.742$$b2013
000063287 591__ $$aMULTIDISCIPLINARY SCIENCES$$b3 / 56 = 0.054$$c2013$$dQ1$$eT1
000063287 655_4 $$ainfo:eu-repo/semantics/review$$vinfo:eu-repo/semantics/publishedVersion
000063287 700__ $$aPalencia, A.
000063287 700__ $$aVirus, C.
000063287 700__ $$aTripathy, A.
000063287 700__ $$aTemple, B.R.
000063287 700__ $$0(orcid)0000-0001-5702-4538$$aVelazquez-Campoy, A.$$uUniversidad de Zaragoza
000063287 700__ $$aCusack, S.
000063287 700__ $$aReader, J.S.
000063287 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDepartamento de Bioquímica y Biología Molecular y Celular$$cBioquímica y Biología Molecular
000063287 773__ $$g4 (2013), 1417 [9 pp]$$pNATURE COMMUNICATIONS$$tNATURE COMMUNICATIONS$$x2041-1723
000063287 8564_ $$s500499$$uhttp://zaguan.unizar.es/record/63287/files/texto_completo.pdf$$yVersión publicada
000063287 8564_ $$s70089$$uhttp://zaguan.unizar.es/record/63287/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000063287 909CO $$ooai:zaguan.unizar.es:63287$$particulos$$pdriver
000063287 951__ $$a2017-11-28-12:45:31
000063287 980__ $$aARTICLE