Protein synthesis inhibitor

Mechanism

Earlier stages

• Rifamycin inhibits prokaryotic DNA transcription into mRNA by inhibiting DNA-dependent RNA polymerase by binding its beta-subunit.

  Initiation

• Linezolid acts at the initiation stage, probably by preventing the formation of the initiation complex, although the mechanism is not fully understood.

  Ribosome assembly

• Aminoglycosides prevent ribosome assembly by binding to the prokaryotic 30S ribosomal subunit.

  Aminoacyl tRNA entry

• Tetracyclines and Tigecycline block the A site on the ribosome, preventing the binding of aminoacyl tRNAs.

  Proofreading

• Aminoglycosides, among other potential mechanisms of action, interfere with the proofreading process, causing increased rate of error in synthesis with premature termination.

  Peptidyl transfer

• Chloramphenicol blocks the peptidyl transfer step of elongation on the 50S ribosomal subunit in both bacteria and mitochondria.
• Macrolides bind to the 50s ribosomal subunits, inhibiting peptidyl transfer.
• Quinupristin/dalfopristin act synergistically, with dalfopristin, enhancing the binding of quinupristin, as well as inhibiting peptidyl transfer. Quinupristin binds to a nearby site on the 50S ribosomal subunit and prevents elongation of the polypeptide, as well as causing incomplete chains to be released.
• Geneticin, also called G418, inhibits the elongation step in both prokaryotic and eukaryotic ribosomes.

  Ribosomal translocation

• Macrolides, clindamycin and aminoglycosides, have evidence of inhibition of ribosomal translocation.
• Fusidic acid prevents the turnover of elongation factor G from the ribosome.
• Ricin inhibits elongation by enzymatically modifying an rRNA of the eukaryotic 60S ribosomal subunit.

  Termination

• Macrolides and clindamycin cause premature dissociation of the peptidyl-tRNA from the ribosome.
• Puromycin has a structure similar to that of the tyrosinyl aminoacyl-tRNA. Thus, it binds to the ribosomal A site and participates in peptide bond formation, producing peptidyl-puromycin. However, it does not engage in translocation and quickly dissociates from the ribosome, causing a premature termination of polypeptide synthesis.
• Streptogramins also cause premature release of the peptide chain.

  Protein synthesis inhibitors of unspecified mechanism

• Retapamulin
• Mupirocin
• Fusidic acid

  Binding site

• Aminoglycosides
• Tetracyclines

• Chloramphenicol
• Clindamycin
• Linezolid
• Macrolides
• Telithromycin
• Streptogramins
• Retapamulin