Journal
NUCLEIC ACIDS RESEARCH
Volume 45, Issue 17, Pages 10284-10292Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkx658
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Funding
- European Research Council [322581]
- United States-Israel Binational Science Foundation [2012007]
- Kimmelman Center for Macromolecular Assemblies
- Adams Fellowship
- Martin S. and Helen Kimmel Professorial Chair at the Weizmann Institute of Science
- European Research Council (ERC) [322581] Funding Source: European Research Council (ERC)
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Antimicrobial resistance within a wide range of pathogenic bacteria is an increasingly serious threat to global public health. Among these pathogenic bacteria are the highly resistant, versatile and possibly aggressive bacteria, Staphylococcus aureus. Lincosamide antibiotics were proved to be effective against this pathogen. This small, albeit important group of antibiotics is mostly active against Gram-positive bacteria, but also used against selected Gram-negative anaerobes and protozoa. S. aureus resistance to lincosamides can be acquired by modifications and/or mutations in the rRNA and rProteins. Here, we present the crystal structures of the large ribosomal subunit of S. aureus in complex with the lincosamides lincomycin and RB02, a novel semisynthetic derivative and discuss the biochemical aspects of the in vitro potency of various lincosamides. These results allow better understanding of the drugs selectivity as well as the importance of the various chemical moieties of the drug for binding and inhibition.
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