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Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria

Author

Listed:
  • Frank Schlünzen

    (Max-Planck-Research, Unit for Ribosomal Structure)

  • Raz Zarivach

    (Weizmann Institute)

  • Jörg Harms

    (Max-Planck-Research, Unit for Ribosomal Structure)

  • Anat Bashan

    (Weizmann Institute)

  • Ante Tocilj

    (Max-Planck-Research, Unit for Ribosomal Structure
    Max-Planck-Institut für Molekulare Genetik)

  • Renate Albrecht

    (Max-Planck-Institut für Molekulare Genetik)

  • Ada Yonath

    (Max-Planck-Research, Unit for Ribosomal Structure
    Weizmann Institute)

  • François Franceschi

    (Max-Planck-Institut für Molekulare Genetik)

Abstract

Ribosomes, the site of protein synthesis, are a major target for natural and synthetic antibiotics. Detailed knowledge of antibiotic binding sites is central to understanding the mechanisms of drug action. Conversely, drugs are excellent tools for studying the ribosome function. To elucidate the structural basis of ribosome–antibiotic interactions, we determined the high-resolution X-ray structures of the 50S ribosomal subunit of the eubacterium Deinococcus radiodurans, complexed with the clinically relevant antibiotics chloramphenicol, clindamycin and the three macrolides erythromycin, clarithromycin and roxithromycin. We found that antibiotic binding sites are composed exclusively of segments of 23S ribosomal RNA at the peptidyl transferase cavity and do not involve any interaction of the drugs with ribosomal proteins. Here we report the details of antibiotic interactions with the components of their binding sites. Our results also show the importance of putative Mg+2 ions for the binding of some drugs. This structural analysis should facilitate rational drug design.

Suggested Citation

  • Frank Schlünzen & Raz Zarivach & Jörg Harms & Anat Bashan & Ante Tocilj & Renate Albrecht & Ada Yonath & François Franceschi, 2001. "Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria," Nature, Nature, vol. 413(6858), pages 814-821, October.
    • Handle: RePEc:nat:nature:v:413:y:2001:i:6858:d:10.1038_35101544
    DOI: 10.1038/35101544
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    Cited by:

    1. Meagan C Small & Pedro Lopes & Rodrigo B Andrade & Alexander D MacKerell Jr, 2013. "Impact of Ribosomal Modification on the Binding of the Antibiotic Telithromycin Using a Combined Grand Canonical Monte Carlo/Molecular Dynamics Simulation Approach," PLOS Computational Biology, Public Library of Science, vol. 9(6), pages 1-14, June.

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