Interaction of avilamycin with ribosomes and resistance caused by mutations in 23S rRNA.
The antibiotic growth promoter avilamycin inhibits protein synthesis by binding to bacterial ribosomes. Here the binding site is further characterized on Escherichia coli ribosomes. The drug interacts with domain V of 23S rRNA, giving a chemical footprint at nucleotides A2482 and A2534. Selection of avilamycin-resistant Halobacterium halobium cells revealed mutations in helix 89 of 23S rRNA. Furthermore, mutations in helices 89 and 91, which have previously been shown to confer resistance to evernimicin, give cross-resistance to avilamycin. These data place the binding site of avilamycin on 23S rRNA close to the elbow of A-site tRNA. It is inferred that avilamycin interacts with the ribosomes at the ribosomal A-site interfering with initiation factor IF2 and tRNA binding in a manner similar to evernimicin.
Kofoed
Christine B
CB
Institute of Molecular Biology, University of Copenhagen, DK-1307 Copenhagen K, Denmark.
Vester
Birte
B
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D018983:DNA Footprinting; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D019617:Halobacterium salinarum / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D009154:Mutation / Q000235:genetics; D009844:Oligosaccharides / Q000378:metabolism / Q000494:pharmacology*; D012338:RNA, Ribosomal, 23S / Q000187:drug effects / Q000235:genetics*; D012270:Ribosomes / Q000187:drug effects*; D012407:rRNA Operon / Q000187:drug effects / Q000235:genetics
D000900:Anti-Bacterial Agents; D009844:Oligosaccharides; D012338:RNA, Ribosomal, 23S; C006653:avilamycin