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

Viomycin and capreomycin belong to the tuberactinomycin family of antibiotics, which are among the most effective antibiotics against multidrug-resistant tuberculosis. Here we present two crystal structures of the 70S ribosome complexed with three tRNAs and bound to either viomycin or capreomycin at 3.3 and 3.5 Å resolution, respectively. Both antibiotics bind to the same site on the ribosome, which lies at the interface between helix 44 (h44) of the small ribosomal subunit and Helix 69 (H69) of the large ribosomal subunit. The structures of these complexes suggest that the tuberactinomycins inhibit translocation by stabilizing the tRNA in the A site in the pre-translocation state. In addition these structures show that the tuberactinomycins bind adjacent to the paromomycin and hygromycin B antibiotics, which may enable the development of new derivatives of tuberactinomycins that are effective against drug resistant strains.