5AH5: Crystal Structure Of The Ternary Complex Of Agrobacterium Radiobacter K84 Agnb2 Leurs-trna-leuams

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.
PDB ID: 5AH5Download
MMDB ID: 136562
PDB Deposition Date: 2015/2/5
Updated in MMDB: 2016/10
Experimental Method:
x-ray diffraction
Resolution: 2.1  Å
Source Organism:
Agrobacterium radiobacter K84
Similar Structures:
Biological Unit for 5AH5: dimeric; determined by author and by software (PISA)
Molecular Components in 5AH5
Label Count Molecule
Protein (1 molecule)
Leucine--trna Ligase
Molecule annotation
Nucleotide(1 molecule)
tRNA-leu TAA Isoacceptor
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

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