Ribosome antibiotic complexes function

Ribosome function is complex numerous cofactors are required for initiation, elongation, and termination (for a detailed description please see ref 33). Independent functions can be ascribed to the two subunits. Peptide bond formation takes place on the 50S subunit within the peptidyl transferase center, whereas decoding of the mRNA takes place on the 308 subunit within the decoding A- and P-sites. tRNAs in the P-site and the A-site span both subunits and couple the two events. After each round of peptide bond formation, a translocation step takes place that involves the movement of the mRNA through the ribosome, transfer of the P-site tRNA to the E (or exit)-site, and transfer of the A-site tRNA to the P-site. Most antibiotics target one of the listed steps decoding at either the A-site or the P-site, peptide bond formation within the peptidyl transferase center, or translocation. 

Although never commercially marketed, nifurquinazole has been shown to be a powerfixl nitrofuran-based bactericidal. Nitrofuran-based antibiotics function by a complex set of mechanisms that result in the degradation of bacterial macromolecules. Rapid reduction of nitrofurans via flavoproteins, specifically nitrofuran reductase, occurs inside the bacterial cell. The highly reactive species that are generated in this process are ultimately responsible for damage to ribosomal proteins and DNA, and they... 

Nishizuka and Lipmann showed that GTP hydrolysis was associated with the function of EFG (presumably accounting for the naming of the factor). This hydrolysis could occur in the absence of translocation and was dependent on the SOS subunit The early studies on the interaction of EFG with ribosomes were carried out by several groups Brot et fit/., Bodley and coworkers and Kaziro and his colleagues. It became apparent that EFG could form a relatively stable complex with ribosomes (specifically the SOS subunit) in the presence of either GTP or GDP. The data suggested that when GTP was used a SOS-EFG-GTP complex was initially formed. This complex was not isolated due to rapid hydrolysis of GTP yielding a SOS-EFG-GDP complex. Presumably, EFG can dissociate from the latter complex and act catalytically with respect to GTP hydrolysis and translocation. A major advance was made by Bodley and coworkers, when they found that the steroid antibiotic, fusidic acid, which was known to be a potent inhibitor of translocation, resulted in the formation of a very stable complex that contained the SOS subunit-EFG GDP fusidic acid. These reactions are shown below. 

Fig. 2.2. Structure of the antibiotic puromycin. Puromycin interrupts the synthesis of the protein chain by mimicing an aminoacyl-tRNA complex, binding to the ribosome, attacking a peptidyl-tRNA (at the P site) with its amino function, but then not undergoing attack by an aminoacyl-tRNA, hence terminating the synthesis. In the upper right corner is shown the adenylic acid terminus of tRNA.

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