Structural insights of lincosamides targeting the ribosome of Staphylococcus aureus

Donna Matzov, Zohar Eyal, Raphael I. Benhamou, Moran Shalev-Benami, Yehuda Halfon, Miri Krupkin, Ella Zimmerman, Haim Rozenberg, Anat Bashan, Micha Fridman, Ada Yonath*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)10284-10292
Number of pages9
JournalNucleic Acids Research
Volume45
Issue number17
DOIs
StatePublished - 1 Sep 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© The Author(s) 2017.

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