The mode of action of thiostrepton in the initiation of protein synthesis.
The inhibition by thiostrepton of the initiation of protein synthesis is exerted at a different level from the inhibition of reactions mediated by EF-Tu and EF-G in the elongation of protein synthesis. The presence of thiostrepton on the 50-S subunit completely prevents the binding of the EF-Tu - GTP - aa-tRNA complex and EF-G - GTP complex to the 70-S ribosome, resulting in cessation of protein synthesis at a concentration of 1 muM thiostrepton. On the other hand, during initiation thiostrepton impairs the coupling of the 50-S subunit with the 30-S initiation complex, indirectly causing inhibition of IF-2-dependent reactions. Impairment of the coupling is strongly influenced by the conditions of incubation. Since formation of formylmethionylpuromycin and the IF-2-dependent GTP hydrolysis are inhibited to the same extent and recycling of IF-2 can take place in the presence of thiostrepton, we conclude that the basic mechanism of inhibition of initiation differs from that of inhibition of elongation.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008715:Methionine; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects*; D010448:Peptide Initiation Factors; D011691:Puromycin; 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; D006160:Guanosine Triphosphate; D012343:RNA, Transfer; D008715:Methionine; D013883:Thiostrepton; D008274:Magnesium