The structures of the anti-tuberculosis antibiotics viomycin and capreomycin bound to the 70S ribosome

摘要

Viomycin and capreomycin belong to the tuberactinomycin family of antibiotics, which are among the most effective antibioticsagainst multidrug-resistant tuberculosis. Here we present two crystal structures of the 70S ribosome in complex with threetRNAs and bound to either viomycin or capreomycin at 3.3- and 3.5-A resolution, respectively. Both antibiotics bind to thesame site on the ribosome, which lies at the interface between helix 44 of the small ribosomal subunit and helix 69 of the largeribosomal subunit. The structures of these complexes suggest that the tuberactinomycins inhibit translocation by stabilizing thetRNA in the A site in the pretranslocation state. In addition, these structures show that the tuberactinomycins bind adjacent tothe binding sites for the paromomycin and hygromycin B antibiotics, which may enable the development of new derivatives oftuberactinomycins that are effective against drug-resistant strains.