Mode of action of bottromycin A2. Release of aminoacyl- or peptidyl-tRNA from ribosomes.
Bottromycin A2 inhibited MS2 phage RNA-dependent protein synthesis as well as polyuridylic acid-(poly(U))- or polyadenylic acid (poly(A))-dependent polypeptide synthesis. When the ribosomal complex with N-acetyl-[14C]phenylalanyl-tRNA (N-acetyl-[14C]Phe-tRNA) at the A site was subjected to bottromycin A2, the release of N-acetyl-[14C]Phe-tRNA was observed while no release of N-acetyl-[14C]Phe-tRNA from the donor site was observed, indicating that the action of bottromycin A2 is specific to the A site of ribosomes. Due to bottromycin's capacity to release [14C]Phe-tRNA or N-acetyl-[14C]Phe-tRNA from the ribosomal acceptor site (A site), bottromycin A2 inhibited the nonenzymatic binding of N-acetyl-[14C]Phe-tRNA and elongation factor T (EF-T)-dependent binding if the concentration of EF-Tu-GTP-[14C]Phe-tRNA ternary complex was low. Our data are consistent with the possibility that the inhibition of overall polypeptide synthesis by bottromycin A2 is at least partly due to bottromycin A2's activity to release aminoacyl- or oligopeptidyl-tRNA from ribosomes. Among 10 antibiotics tested, bottromycin A2 and lincomycin released aminoacyl-tRNA from ribosomes.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000494:pharmacology*; D001665:Binding Sites; D003090:Coliphages / Q000187:drug effects / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008034:Lincomycin / Q000494:pharmacology; D010649:Phenylalanine; D014176:Protein Biosynthesis / Q000187:drug effects*; D012343:RNA, Transfer / Q000378:metabolism*; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010649:Phenylalanine; D012343:RNA, Transfer; D008034:Lincomycin; D004229:Dithiothreitol