Single-molecule study of viomycin's inhibition mechanism on ribosome translocation.

Abstract

Viomycin belongs to the tuberactinomycin family of antibiotics against tuberculosis. However, its inhibition mechanism remains elusive. Although it is clear that viomycin inhibits the ribosome intersubunit ratcheting, there are contradictory reports about whether the antibiotic viomycin stabilizes the tRNA hybrid or classical state. By using a single-molecule FRET method to directly observe the tRNA dynamics relative to ribosomal protein L27, we have found that viomycin trapped the hybrid state within certain ribosome subgroups but did not significantly suppress the tRNA dynamics. The persistent fluctuation of tRNA implied that tRNA motions were decoupled from the ribosome intersubunit ratcheting. Viomycin also promoted peptidyl-tRNA fluctuation in the posttranslocation complex, implying that, in addition to acylated P-site tRNA, the decoding center also played an important role of ribosome locking after translocation. Therefore, viomycin inhibits translocation by trapping the hybrid state in the pretranslocation complex and disturbing the stability of posttranslocation complex. Our results imply that ribosome translocation is possibly a synergistic process of multiple decoupled local dynamics.

• Authors: Cindy T Ly, Mediha E Altuntop, Yuhong Wang
• Journal: Biochemistry (Biochemistry) Vol. 49 Issue 45 Pg. 9732-8 (Nov 16 2010) ISSN: 1520-4995 [Electronic] United States
• PMID: 20886842 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Oligopeptides
• Peptide Elongation Factor G
• RNA, Messenger
• RNA, Transfer
• Viomycin

Topics

• Biological Transport (drug effects)
• Fluorescence Resonance Energy Transfer (methods)
• Oligopeptides (biosynthesis, metabolism)
• Peptide Elongation Factor G (genetics, metabolism)
• Protein Biosynthesis (drug effects)
• Protein Transport
• RNA, Messenger (genetics)
• RNA, Transfer (drug effects, genetics)
• Ribosomes (drug effects, genetics, metabolism)
• Translocation, Genetic (drug effects)
• Viomycin (pharmacology)