https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2874%2980689-7

Inhibitors of protein synthesis

Studies on Polypeptide Elongation Factors from Escherichia coli II. PURIFICATION OF FACTORS Tu-GUANOSINE DIPHOSPHATE, Ts, AND Tu-Ts, AND CRYSTALLIZATION OF Tu-GUANOSINE DIPHOSPHATE AND Tu-Ts

Studies on the purification and properties of factor Tu from E. coli.

Kirromycin, a new inhibitor of protein synthesis, is shown to interfere with the peptide transfer reaction by acting on elongation factor Tu (EF-Tu). All the reactions associated with this elongation factor are affected. Formation of the EF-Tu·GTP complex is strongly stimulated. Peptide bond formation is prevented only when Phe-tRNAPhe is bound enzymatically to ribosomes, presumably because GTP hydrolysis associated with enzymatic binding of Phe-tRNAPhe is not followed by release of EF-Tu·GDP from the ribosome. This antibiotic also enables EF-Tu to catalyze the binding of Phe-tRNAPhe to the poly(U)·ribosome complex even in the absence of GTP. EF-Tu activity in the GTPase reaction is dramatically affected by kirromycin: GTP hydrolysis, which normally requires ribosomes and aminoacyl-tRNA, takes place with the elongation factor alone. This GTPase shows the same Km for GTP as the one dependent on Phe-tRNAPhe and ribosomes in the absence of the antibiotic. Ribosomes and Phe-tRNAPhe, but not tRNAPhe or Ac-Phe-tRNAPhe, stimulate the kirromycin-induced EF-Tu GTPase. These results indicate that the catalytic center of EF-Tu GTPase that is dependent upon aminoacyl-tRNA and ribosomes is primarily located on the elongation factor. In conclusion, kirromycin can substitute for GTP, aminoacyl-tRNA, or ribosomes in various reactions involving EF-Tu, apparently by affecting the allosteric controls between the sites on the EF-Tu molecule interacting with these components.

https://www.pnas.org/content/pnas/71/12/4910.full.pdf

Kirromycin, an inhibitor of protein biosynthesis that acts on elongation factor Tu.

https://mmbr.asm.org/content/mmbr/33/2/264.full.pdf

Charles W. Garner

Papers

Formation and properties of the aminoacyl transfer ribonucleic acid-guanosine triphosphate-protein complex.

The Role of an Aminoacyl-tRNA-GTP-Protein Complex in Polypeptide Synthesis