Kirromycin, an inhibitor of protein biosynthesis that acts on elongation factor Tu.
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-tRNA(Phe) is bound enzymatically to ribosomes, presumably because GTP hydrolysis associated with enzymatic binding of Phe-tRNA(Phe) is not followed by release of EF-Tu.GDP from the ribosome. This antibiotic also enables EF-Tu to catalyze the binding of Phe-tRNA(Phe) 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 K(m) for GTP as the one dependent on Phe-tRNA(Phe) and ribosomes in the absence of the antibiotic. Ribosomes and Phe-tRNA(Phe), but not tRNA(Phe) or Ac-Phe-tRNA(Phe), 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.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D003864:Depression, Chemical; D004926:Escherichia coli / Q000378:metabolism; D005663:Furans / Q000494:pharmacology; D006151:Guanosine; D006160:Guanosine Triphosphate / Q000378:metabolism; D010441:Peptide Chain Elongation, Translational / Q000187:drug effects*; D010445:Peptide Elongation Factors; D010649:Phenylalanine; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D011728:Pyridones / Q000494:pharmacology; D012343:RNA, Transfer / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D014316:Tritium
D000900:Anti-Bacterial Agents; D002250:Carbon Radioisotopes; D005663:Furans; D010445:Peptide Elongation Factors; D010761:Phosphorus Radioisotopes; D011728:Pyridones; D014316:Tritium; D006151:Guanosine; D010649:Phenylalanine; D006160:Guanosine Triphosphate; D012343:RNA, Transfer; D010744:Phosphoric Monoester Hydrolases; C008536:mocimycin