Antibiotic inhibition of translation

See also Internal Ribosomal Structure, Translation. Initiation of Translation, Elongation of Translation, Termination of Translation, Antibiotic Inhibition of Translation, Genetic Code, Codons... 

See also Antibiotic Inhibition of Translation, Translation Overview, Structure of tRNAs, Eukaryotic vs Prokaryotic Translation... 

What could be the signal for the induction of the cold shock proteins It has been observed that shifting E. coli cells from 37 to 5 °C results in an accumulation of 70S monosomes with a concomitant decrease in the number of polysomes [129]. Further, it has been shown that a cold shock response is induced when ribosomal function is inhibited, e.g. by cold-sensitive ribosomal mutations [121] or by certain antibiotics such as chloramphenicol [94]. These data indicate that the physiological signal for the induction of the cold shock response is inhibition of translation caused by the abrupt shift to lower temperature. Then, the cold shock proteins RbfA, CsdA and IF2 associate with the 70S ribosomes to convert the cold-sensitive nontranslatable ribosomes into cold-resistant translatable ribosomes. This in turn results in an increase in cellular protein synthesis and growth of the cells. 

The three antibiotic inhibitors of translation that will be used in this experiment are chloramphenicol, cycloheximide, and puromycin (Fig. 23-10). Chloramphenicol is specific for prokaryotic ribosomes, blocking the transfer of the peptide on the tRNA at the P site to the amino acid linked to the tRNA at the A site (the peptidyl transfer reaction). Since the source of the ribosomes used in this experiment is wheat germ (eukaryotic), we would predict that chloramphenicol would not have a great effect on translation. The mechanism of cycloheximide-mediated inhibition is the same as that described above for chloramphenicol, except for the fact that it is specific for the 80S eukaryotic ribosome. Puromycin is a more broad translational inhibitor, effective on both eukaryotic and prokaryotic ribosomes. It acts as a substrate analog of aminoacyl tRNA. When it binds at the A site of the ribosome, it induces premature termination of translation (Fig. 

Champney, W. S. (1998). Inhibition of translation and 50S ribosomal subunit formation in S. aureus all by 11 different ketolide antibiotics. Curr. Microbiol. 37,418-425. 

Greenberg, W.C. et al.. Design and synthesis of new aminoglycoside antibiotics containing neamine as an optimal core structure correlation of antibiotic activity with in vitro inhibition of translation, J. Am. Chem. Soc., 121, 6527, 1999. 

Brandi, L., Fabbretti, A., La Teana, A., Abbondi, M., Losi, D., Donadio, S., and Gualerzi, C. O. (2006b). Specific, efficient, and selective inhibition of prokaryotic translation initiation by a novel peptide antibiotic. Proc. Nat. Acad. Sci. USA 103, 39-44. 

Macrolide antibiotics consist of a central lactone ring from which extend various functional groups and sugar substituents (Fig. 4.6). Macrolides are divided into three subgroups depending on the number of atoms in the lactone ring 14-mem-bered, 15-membered and 16-membered. Inhibition of protein translation by macrolides has two distinct characteristics. Firstly, macrolides will neither bind to... 

The prototypical aminoacylated nucleoside analogue antibiotic is puromycin which inhibits the protein translation in all three domains of life. The chemical structure of puromycin is the same as that of tyrosylated adenosine, except for the presence of three added methyl groups and the replacement of an ester bond with an amide bond (Fig. 4.11). Puromycin mimics tyrosyl-tRNA so well that it binds to the A-site and gets incorporated into an elongating peptide. This leads to termination of translation because puromycin terminated peptides fall off the ribosome. Puromycin derivatives have been used crystallographically as peptidyl transferase substrates and have contributed to our understanding of the structure of the peptidyl transferase site (Fig. 4.5) [11, 16, 45],... 

The result is the immediate termination of translation and the release of a truncated protein. Two potent antibiotics that specifically inhibit bacterial translation, are tetracycline, which blocks the A site and prevents the entry of aminoacyl-tRNAs, and chloramphenicol, which inhibits the peptidyl transferase activity of the 23 S rRNA. The mechanisms of action of these antibiotics, including streptomycin, which alters the fidelity of translation in bacteria, are listed in Table 26.1. 

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