The mode of action of thiostrepton in the initiation of protein synthesis

Eur J Biochem. 1976 Nov 1;70(1):39-47. doi: 10.1111/j.1432-1033.1976.tb10953.x.


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.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Escherichia coli / metabolism
  • Guanosine Triphosphate / metabolism
  • Kinetics
  • Magnesium / pharmacology
  • Methionine
  • Peptide Chain Initiation, Translational / drug effects*
  • Peptide Initiation Factors*
  • Puromycin
  • RNA, Transfer / metabolism
  • Ribosomes / drug effects
  • Ribosomes / metabolism
  • Temperature
  • Thiostrepton / pharmacology*


  • Anti-Bacterial Agents
  • Peptide Initiation Factors
  • Puromycin
  • Guanosine Triphosphate
  • RNA, Transfer
  • Methionine
  • Thiostrepton
  • Magnesium