Enacyloxin IIa, an inhibitor of protein biosynthesis that acts on elongation factor Tu and the ribosome.

摘要: This work analyzes the action of enacyloxin Ila, an inhibitor bacterial protein biosynthesis. Enacyloxin IIa [IC50 on poly(Phe) synthesis approximately 70 nM] is shown to affect interaction between elongation factor (EF) Tu and GTP or GDP; in particular, dissociation EF-Tu-GTP strongly retarded, causing Kd EF- Tu-GTP decrease from 500 0.7 nM. In its presence, migration velocity both GTP- GDP-bound EF-Tu native PAGE increased. The stimulation EF-Tu-GDP by EF-Ts inhibited. can still form a stable complex with aminoacyl-tRNA (aa-tRNA), but it no longer protects aa-tRNA against spontaneous deacylation, showing that orientation respect 3' end modified. However, EF-Tu-dependent binding ribosomal A-site impaired only slightly antibiotic activity peptidyl-transferase center, as determined puromycin reactivity, not affected. contrast, C-terminal incorporation Phe into poly(Phe)-tRNA bound P-site inhibited, effect observed if Phe-tRNA nonenzymatically well. Thus, directly, inducing anomalous positioning aa-tRNA, inhibits amino acid polypeptide chain. Therefore, first found have dual specificity targeted ribosome.