Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 41 (5), 1091-9

The Pleuromutilin Drugs Tiamulin and Valnemulin Bind to the RNA at the Peptidyl Transferase Centre on the Ribosome

Affiliations

The Pleuromutilin Drugs Tiamulin and Valnemulin Bind to the RNA at the Peptidyl Transferase Centre on the Ribosome

S M Poulsen et al. Mol Microbiol.

Abstract

The pleuromutilin antibiotic derivatives, tiamulin and valnemulin, inhibit protein synthesis by binding to the 50S ribosomal subunit of bacteria. The action and binding site of tiamulin and valnemulin was further characterized on Escherichia coli ribosomes. It was revealed that these drugs are strong inhibitors of peptidyl transferase and interact with domain V of 23S RNA, giving clear chemical footprints at nucleotides A2058-9, U2506 and U2584-5. Most of these nucleotides are highly conserved phylogenetically and functionally important, and all of them are at or near the peptidyl transferase centre and have been associated with binding of several antibiotics. Competitive footprinting shows that tiamulin and valnemulin can bind concurrently with the macrolide erythromycin but compete with the macrolide carbomycin, which is a peptidyl transferase inhibitor. We infer from these and previous results that tiamulin and valnemulin interact with the rRNA in the peptidyl transferase slot on the ribosomes in which they prevent the correct positioning of the CCA-ends of tRNAs for peptide transfer.

Similar articles

See all similar articles

Cited by 27 PubMed Central articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback