Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.1.1.4 (leucyl-tRNA synthetase)
 297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Crops can be devastated by pathogenic strains of Agrobacterium tumefaciens that cause crown gall tumors. This devastation can be prevented by the nonpathogenic biocontrol agent A. radiobacter K84, which prevents disease by production of the "Trojan horse" toxin agrocin 84, which is specifically imported into tumorgenic A. tumefaciens strains to cause cell death. We demonstrate that this biocontrol agent targets A. tumefaciens leucyl-tRNA synthetase (LeuRS), an essential enzyme for cell viability, while the agent itself survives by having a second, self-protective copy of the synthetase. In principle, this strategy from nature could be applied to other crop diseases by direct intervention.
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PMID:Major biocontrol of plant tumors targets tRNA synthetase. 1614 Oct 66

Antibiotic-producing microbes evolved self-resistance mechanisms to avoid suicide. The biocontrol Agrobacterium radiobacter K84 secretes the Trojan Horse antibiotic agrocin 84 that is selectively transported into the plant pathogen A. tumefaciens and processed into the toxin TM84. We previously showed that TM84 employs a unique tRNA-dependent mechanism to inhibit leucyl-tRNA synthetase (LeuRS), while the TM84-producer prevents self-poisoning by expressing a resistant LeuRS AgnB2. We now identify a mechanism by which the antibiotic-producing microbe resists its own toxin. Using a combination of structural, biochemical and biophysical approaches, we show that AgnB2 evolved structural changes so as to resist the antibiotic by eliminating the tRNA-dependence of TM84 binding. Mutagenesis of key resistance determinants results in mutants adopting an antibiotic-sensitive phenotype. This study illuminates the evolution of resistance in self-immunity genes and provides mechanistic insights into a fascinating tRNA-dependent antibiotic with applications for the development of anti-infectives and the prevention of biocontrol emasculation.
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PMID:Structural characterization of antibiotic self-immunity tRNA synthetase in plant tumour biocontrol agent. 2771 2