The cyclic octapeptide antibiotic argyrin B inhibits translation by trapping EF-G on the ribosome during translocation

Maximiliane Wieland, Mikael Holm, Emily J. Rundlet, Martino Morici, Timm O. Koller, Tinashe P. Maviza, Domen Pogorevc, Ilya A. Osterman, Rolf Müller, Scott C. Blanchard, Daniel N. Wilson

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

SignificanceThe increase in multidrug-resistant bacteria highlights the urgent need for compounds with novel target sites that can be developed as antibiotics. The argyrins represent a family of naturally produced octapeptides that display promising activity against Pseudomonas aeruginosa by inhibiting protein synthesis. Our structural and kinetic analyses reveal that argyrins inhibit protein synthesis by interacting with, and trapping, the translation elongation factor G (EF-G) on the ribosome, analogous to that reported previously for the unrelated antibiotic fusidic acid. However, the binding site of argyrin on EF-G is distinct from that of fusidic acid, indicating that intramolecular movements at the domain III/V interface of EF-G are also essential for facilitating late events in the translocation mechanism.

Original languageEnglish
Pages (from-to)e2114214119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number19
DOIs
Publication statusPublished - 10 May 2022

Keywords

  • antibiotic
  • argyrin
  • fusidic acid
  • ribosome
  • translocation

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