Structural insights of lincosamides targeting the ribosome of Staphylococcus aureus.

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Matzov D, Eyal Z, Benhamou RI, Shalev-Benami M, Halfon Y, Krupkin M, Zimmerman E, Rozenberg H, Bashan A, Fridman M, Yonath A

Structural insights of lincosamides targeting the ribosome of Staphylococcus aureus.

Nucleic Acids Res. 2017 Sep 29;45(17):10284-10292. doi: 10.1093/nar/gkx658.

PubMed ID

28973455 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drugs

Lincomycin

Drug Targets

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