Antibacterial peptide Microcin J25 inhibits transcription by binding within and obstructing the RNA polymerase secondary channel

Jayanta Mukhopadhyay, Elena Sineva, Jennifer Knight, Ronald M. Levy, Richard H. Ebright

Research output: Contribution to journalArticlepeer-review

151 Scopus citations

Abstract

The antibacterial peptide microcin J25 (MccJ25) inhibits transcription by bacterial RNA polymerase (RNAP). Biochemical results indicate that inhibition of transcription occurs at the level of NTP uptake or NTP binding by RNAP. Genetic results indicate that inhibition of transcription requires an extensive determinant, comprising more than 50 amino acid residues, within the RNAP secondary channel (also known as the "NTP-uptake channel" or "pore"). Biophysical results indicate that inhibition of transcription involves binding of MccJ25 within the RNAP secondary channel. Molecular modeling indicates that binding of MccJ25 within the RNAP secondary channel obstructs the RNAP secondary channel. We conclude that MccJ25 inhibits transcription by binding within and obstructing the RNAP secondary channel - acting essentially as a "cork in a bottle." Obstruction of the RNAP secondary channel represents an attractive target for drug discovery.

Original languageEnglish (US)
Pages (from-to)739-751
Number of pages13
JournalMolecular cell
Volume14
Issue number6
DOIs
StatePublished - Jun 18 2004

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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