The antibacterial threaded-lasso peptide capistruin inhibits bacterial RNA polymerase

Konstantin Kuznedelov, Ekaterina Semenova, Thomas A. Knappe, Damir Mukhamedyarov, Aashish Srivastava, Sujoy Chatterjee, Richard H. Ebright, Mohamed A. Marahiel, Konstantin Severinov

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Capistruin, a ribosomally synthesized, post-translationally modified peptide produced by Burkholderia thailandensis E264, efficiently inhibits growth of Burkholderia and closely related Pseudomonas strains. The functional target of capistruin is not known. Capistruin is a threaded-lasso peptide (lariat peptide) consisting of an N-terminal ring of nine amino acids and a C-terminal tail of 10 amino acids threaded through the ring. The structure of capistruin is similar to that of microcin J25 (MccJ25), a threaded-lasso antibacterial peptide that is produced by some strains of Escherichia coli and targets DNA-dependent RNA polymerase (RNAP). Here, we show that capistruin, like MccJ25, inhibits wild type E. coli RNAP but not mutant, MccJ25-resistant, E. coli RNAP. We show further that an E. coli strain resistant to MccJ25, as a result of a mutation in an RNAP subunit gene, exhibits resistance to capistruin. The results indicate that the structural similarity of capistruin and MccJ25 reflects functional similarity and suggest that the functional target of capistruin, and possibly other threaded-lasso peptides, is bacterial RNAP.

Original languageEnglish (US)
Pages (from-to)842-848
Number of pages7
JournalJournal of molecular biology
Volume412
Issue number5
DOIs
StatePublished - Oct 7 2011

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Keywords

  • RNA polymerase
  • RNA polymerase inhibitor
  • capistruin
  • lariat peptides
  • microcin J25 (MccJ25)

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