Structures of the Escherichia coli ribosome with antibiotics bound near the peptidyl transferase center explain spectra of drug action
10.1073/pnas.1007988107
Crossref journal-article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences (341)
Abstract

Differences between the structures of bacterial, archaeal, and eukaryotic ribosomes account for the selective action of antibiotics. Even minor variations in the structure of ribosomes of different bacterial species may lead to idiosyncratic, species-specific interactions of the drugs with their targets. Although crystallographic structures of antibiotics bound to the peptidyl transferase center or the exit tunnel of archaeal ( Haloarcula marismortui ) and bacterial ( Deinococcus radiodurans ) large ribosomal subunits have been reported, it remains unclear whether the interactions of antibiotics with these ribosomes accurately reflect those with the ribosomes of pathogenic bacteria. Here we report X-ray crystal structures of the Escherichia coli ribosome in complexes with clinically important antibiotics of four major classes, including the macrolide erythromycin, the ketolide telithromycin, the lincosamide clindamycin, and a phenicol, chloramphenicol, at resolutions of ∼3.3  Å –3.4  Å . Binding modes of three of these antibiotics show important variations compared to the previously determined structures. Biochemical and structural evidence also indicates that interactions of telithromycin with the E. coli ribosome more closely resembles drug binding to ribosomes of bacterial pathogens. The present data further argue that the identity of nucleotides 752, 2609, and 2055 of 23S ribosomal RNA explain in part the spectrum and selectivity of antibiotic action.

Bibliography

Dunkle, J. A., Xiong, L., Mankin, A. S., & Cate, J. H. D. (2010). Structures of the Escherichia coli ribosome with antibiotics bound near the peptidyl transferase center explain spectra of drug action. Proceedings of the National Academy of Sciences, 107(40), 17152–17157.

Authors 4
  1. Jack A. Dunkle (first)
  2. Liqun Xiong (additional)
  3. Alexander S. Mankin (additional)
  4. Jamie H. D. Cate (additional)
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Dates
Type When
Created 14 years, 11 months ago (Sept. 28, 2010, 12:45 a.m.)
Deposited 3 years, 2 months ago (June 7, 2022, 3:04 a.m.)
Indexed 2 weeks ago (Aug. 21, 2025, 2:21 p.m.)
Issued 14 years, 11 months ago (Sept. 27, 2010)
Published 14 years, 11 months ago (Sept. 27, 2010)
Published Online 14 years, 11 months ago (Sept. 27, 2010)
Published Print 14 years, 11 months ago (Oct. 5, 2010)
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@article{Dunkle_2010, title={Structures of the Escherichia coli ribosome with antibiotics bound near the peptidyl transferase center explain spectra of drug action}, volume={107}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1007988107}, DOI={10.1073/pnas.1007988107}, number={40}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Dunkle, Jack A. and Xiong, Liqun and Mankin, Alexander S. and Cate, Jamie H. D.}, year={2010}, month=sep, pages={17152–17157} }