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

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Schlunzen F, Zarivach R, Harms J, Bashan A, Tocilj A, Albrecht R, Yonath A, Franceschi F

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

Nature. 2001 Oct 25;413(6858):814-21.

PubMed ID

11677599 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Erythromycin	23S ribosomal RNA	Nucleotide	Enteric bacteria and other eubacteria	Yes	Inhibitor	Details

Polypeptides

Name	UniProt ID
50S ribosomal protein L32	P49228	Details