Plant tumour biocontrol agent employs a tRNA-dependent mechanism to inhibit leucyl-tRNA synthetase

Chopra, S. ; Palencia, A. ; Virus, C. ; Tripathy, A. ; Temple, B.R. ; Velazquez-Campoy, A. (Universidad de Zaragoza) ; Cusack, S. ; Reader, J.S.

Resumen: Leucyl-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.

Idioma: Inglés

DOI: 10.1038/ncomms2421

Año: 2013

Publicado en: NATURE COMMUNICATIONS 4 (2013), 1417 [9 pp]
ISSN: 2041-1723

Factor impacto JCR: 10.742 (2013)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 3 / 56 = 0.054 (2013) - Q1 - T1

Tipo y forma: Revisión (Versión definitiva)

Área (Departamento): Bioquímica y Biología Molecular (Departamento de Bioquímica y Biología Molecular y Celular)