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

Frank Schlünzen, Raz Zarivach, Jörg Harms, Anat Bashan, Ante Tocilj, Renate Albrecht, Ada Yonath, François Franceschi

Research output: Contribution to journalArticlepeer-review

908 Scopus citations

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 fo 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.

Original languageEnglish
Pages (from-to)814-821
Number of pages8
JournalNature
Volume413
Issue number6858
DOIs
StatePublished - 25 Oct 2001
Externally publishedYes

ASJC Scopus subject areas

  • General

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