Figure 11.12. Gougerotin (upper) and amicetin (lower).

substrates and PTC of the ribosome. It is remarkable that the binding of the antibiotics stimulates the interaction of the low-molecular-mass analogs of the donor substrate with PTC. These antibiotics compete with each other and seem to possess a similar mechanism of action.

Mutations conferring the resistance to amicetin were found in the position U2438 of 23S RNA that is close to, but not within, the PTC ring. This position do not coincide with the positions of drug resistance mutations in the cases of the other antibiotic groups described above. An interesting fact is that no protection of the 23S RNA residues by the antibiotic of this group, blasticidin S, has been observed in the corresponding foot-printing experiments. Thus, the mechanism of action of the antibiotics under consideration seems to be different from that of the above-described groups of lincosamides, macrolides and streptogramin B, and may be truly competitive.


This is a very potent, broad-spectrum antibiotic affecting both prokaryotic (including archaebacterial) and eukaryotic systems. It strongly inhibits peptidyl transferase activity of 70S and 80S ribosomes or their isolated large subunits. The chemical structure of sparsomycin (Fig. 11.13) shows that it contains pyrimidine residue, amide group and sulfoxide group that may be relevant to its inhibitory activity. The mode of action of the drug is unusual and different from that of the above-metioned antibiotics. First of all, the antibiotic is uncapable of binding to ribosomes in the absense of the donor substrate (peptidyl-tRNA or its truncated derivatives), i.e. it seems to lack an affinity to ribosomal elements per se. The bindings of the antibiotic and the donor substrate are synergistic; the drug stimulates the binding of the donor substrate to the ribosome and fixes it in the J site of PTC. It is possible that the antibiotic forms a ternary complex with the donor substrate and PTC. When bound, the antibiotic blocks or weakens the interaction of the acceptor substrate (aminoacyl-tRNA or puromycin) with PTC. It is possible that the antibiotic bound with the peptidyl-tRNA-carrying ribosome overlaps the a site of PTC and thus prevents the acceptor substrate binding. Alternatively, it may be hypothesized that sparsomycin fixes the donor substrate, with which it strongly interacts within PTC, in its original conformation and prevents the formation of the transition complex (tetrahedral intermediate), thus blocking the stage A ® B in Fig. 11.5.


This antibiotic (Fig. 11.14) inhibits transpeptidation specifically in eukaryotic ribosomes, as well as in archaebacterial ribosomes. It binds to the 60S ribosomal subunit in the region of PTC. It is apparent that anisomycin interferes with the interaction of the acceptor substrate with PTC. It inhibits puromycin reaction on eukaryotic ribosomes and their isolated 60S subunits in vitro. In vivo anisomycin is a powerful inhibitor of transpeptidation step and may block elongation completely, arresting the movement of ribosomes along the mRNA and thereby "freezing" the polyribosomes. Generally, this antibiotic can be considered as the eukaryotic equivalent of chloramphenicol. Indeed, mutations conferring resistance to anisomycin have been identified in the ribosomal RNA section within the PTC ring coinciding with that in the case of the resistance to chloramphenicol: the mutation positions are equivalent to G2447, C2452, and A2453 of eubacterial 23S RNA.

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