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

Article Details

Citation

Copy to clipboard

Stanley RE, Blaha G, Grodzicki RL, Strickler MD, Steitz TA

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

Nat Struct Mol Biol. 2010 Mar;17(3):289-93. doi: 10.1038/nsmb.1755. Epub 2010 Feb 14.

PubMed ID

20154709 [ View in PubMed

]

Abstract

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 in complex with three tRNAs and bound to either viomycin or capreomycin at 3.3- and 3.5-A resolution, respectively. Both antibiotics bind to the same site on the ribosome, which lies at the interface between helix 44 of the small ribosomal subunit and helix 69 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 pretranslocation state. In addition, these structures show that the tuberactinomycins bind adjacent to the binding sites for the paromomycin and hygromycin B antibiotics, which may enable the development of new derivatives of tuberactinomycins that are effective against drug-resistant strains.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Viomycin	16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA	Protein	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Yes	Inhibitor	Details