SnapShot: Antibiotic Inhibition of Protein Synthesis I

Aminoglycosides Apramycin, gentamycin, hygromycin B, kanamycin, neomycin, paromomycin, tobramycinElongation (translocation) Most aminoglycoside antibiotics induce translational misreading by promoting binding of near-cognate tRNAs, but the biological effect is probably due to inhibition of the translocation reaction and promotion of back-translocation.Edeine Edeine A Initiation (fMet-tRNA binding) Edeine prevents binding of the initiator tRNA to the 30S subunit in an mRNA-dependent manner.GE81112 GE81112 Initiation (fMet-tRNA binding)GE81112 inhibits binding of the initiator tRNA to the 30S subunit in an mRNA-independent manner.Kasugamycin Kasugamycin Initiation (fMet-tRNA binding) Kasugamycin inhibits translation initiation of canonical mRNAs by binding in the path of the mRNA and preventing stable interaction of the initiator tRNA with the start codon. Pactamycin Pactamycin Initiation, elongation (translocation) Early data suggest that pactamycin allows 30S but not 70S initiation complex formation, whereas recently pactamycin was shown to inhibit translocation in a tRNA-mRNA-dependent manner.Spectinomycin Spectinomycin Elongation (translocation) Spectinomycin binds to the neck of the small subunit and prevents the relative movement of the head and body that is needed for the completion of translocation. Streptomycin Streptomycin Elongation (misreading) Streptomycin increases affinity of tRNA for the A site, has a modest inhibitory effect on translocation, promotes back-translocation, and induces high-level translational misreading.Tetracyclines/glycylcyclines Doxycycline, minocycline, tetracycline/tigecyclineElongation (tRNA delivery) Tetracyclines prevent stable binding of the EF-Tu-tRNA-GTP ternary complex to the ribosome and inhibit accommodation of A-tRNAs upon EF-Tu-dependent GTP hydrolysis.Viomycin Capreomycin, viomycin Elongation (translocation) Viomycin locks tRNAs in a hybrid-site translocation intermediate state, preventing conversion by EF-G into a posttranslocation state.