4FN5: Elongation Factor G 1 (Pseudomonas Aeruginosa) In Complex With Argyrin B

Argyrins, produced by myxobacteria and actinomycetes, are cyclic octapeptides with antibacterial and antitumor activity. Here, we identify elongation factor G (EF-G) as the cellular target of argyrin B in bacteria, via resistant mutant selection and whole genome sequencing, biophysical binding studies and crystallography. Argyrin B binds a novel allosteric pocket in EF-G, distinct from the known EF-G inhibitor antibiotic fusidic acid, revealing a new mode of protein synthesis inhibition. In eukaryotic cells, argyrin B was found to target mitochondrial elongation factor G1 (EF-G1), the closest homologue of bacterial EF-G. By blocking mitochondrial translation, argyrin B depletes electron transport components and inhibits the growth of yeast and tumor cells. Further supporting direct inhibition of EF-G1, expression of an argyrin B-binding deficient EF-G1 L693Q variant partially rescued argyrin B-sensitivity in tumor cells. In summary, we show that argyrin B is an antibacterial and cytotoxic agent that inhibits the evolutionarily conserved target EF-G, blocking protein synthesis in bacteria and mitochondrial translation in yeast and mammalian cells.
PDB ID: 4FN5Download
MMDB ID: 103350
PDB Deposition Date: 2012/6/19
Updated in MMDB: 2012/09
Experimental Method:
x-ray diffraction
Resolution: 2.9  Å
Source Organism:
Similar Structures:
Biological Unit for 4FN5: dimeric; determined by author and by software (PISA)
Molecular Components in 4FN5
Label Count Molecule
Protein (1 molecule)
Elongation Factor G 1(Gene symbol: fusA1)
Molecule annotation
Nucleotide(1 molecule)
Argyrin B
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB