The pleuromutilin drugs tiamulin and valnemulin bind to the RNA at the peptidyl transferase centre on the ribosome

Citation
Sm. Poulsen et al., The pleuromutilin drugs tiamulin and valnemulin bind to the RNA at the peptidyl transferase centre on the ribosome, MOL MICROB, 41(5), 2001, pp. 1091-1099
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Microbiology
Journal title
MOLECULAR MICROBIOLOGY
ISSN journal
0950-382X → ACNP
Volume
41
Issue
5
Year of publication
2001
Pages
1091 - 1099
Database
ISI
SICI code
0950-382X(200109)41:5<1091:TPDTAV>2.0.ZU;2-G
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 characterize d on Escherichia coli ribosomes. It was revealed that these drugs are stron g 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 funct ionally important, and all of them are at or near the peptidyl transferase centre and have been associated with binding of several antibiotics. Compet itive 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 previou s results that tiamulin and valnemulin interact with the rRNA in the peptid yl transferase slot on the ribosomes in which they prevent the correct posi tioning of the CCA-ends of tRNAs for peptide transfer.