The joining of the 30-S initiation complex with the 50-S subunit, the main target for thiostrepton.
The study undertaken in this paper on the mode of action of thiostrepton provides data which permit a more precise localization of the main target of thiostrepton. There is severe impairment of the joining of the 50-S subunit, probably carrying thiostrepton, with either the 30-S subunit or the 30-S initiation complex. The degree of impairment of this coupling is temperature dependent, being almost completely inhibited at 0 degrees C, whereas at 37 degrees C the effect is much less marked, provided that natural messenger RNA is present. The inhibition of initiation by thiostrepton is more severe in the presence of IF-1, a factor, which similar to thiostrepton, is able to shift the dynamic equilibrium of 70-S in equilibrium 50-S + 30-S more towards dissociation. By means of 14C-labeled IF-2 it is demonstrated that the binding of IF-2 into the 70-S initiation complex is prevented by thiostrepton, which seems to be the main cause for non-coupling.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001665:Binding Sites; D004926:Escherichia coli / Q000378:metabolism; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects; D010448:Peptide Initiation Factors; D011691:Puromycin / Q000494:pharmacology; D012343:RNA, Transfer / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism*; D013696:Temperature; D013883:Thiostrepton / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D010448:Peptide Initiation Factors; D011691:Puromycin; D012343:RNA, Transfer; D008715:Methionine; D013883:Thiostrepton