The Structure of the Anti-tuberculosis Antibiotics Viomycin and Capreomycin Bound to the 70S Ribosome

Journal Article · Fri Jan 01 04:00:00 EST 2010 · Nature Structural and Molecular Biology

DOI:https://doi.org/10.1038/nsmb.1755· OSTI ID:1019896

Stanley, R; Blaha, G; Grodzicki, R; Strickler, M; Steitz, T

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-{angstrom} 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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: DOE - OFFICE OF SCIENCE
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 1019896
• Report Number(s): BNL--95742-2011-JA
• Journal Information: Nature Structural and Molecular Biology, Journal Name: Nature Structural and Molecular Biology Journal Issue: 3 Vol. 17; ISSN 1545-9993
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIBIOTICS
CRYSTAL STRUCTURE
RESOLUTION
RIBOSOMES
STRAINS
TRANSLOCATION
TUBERCULOSIS
national synchrotron light source