The site of action of oxazolidinone antibiotics in living bacteria and in human mitochondria.
Article Details
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Leach KL, Swaney SM, Colca JR, McDonald WG, Blinn JR, Thomasco LM, Gadwood RC, Shinabarger D, Xiong L, Mankin AS
The site of action of oxazolidinone antibiotics in living bacteria and in human mitochondria.
Mol Cell. 2007 May 11;26(3):393-402. doi: 10.1016/j.molcel.2007.04.005.
- PubMed ID
- 17499045 [ View in PubMed]
- Abstract
The oxazolidinones are one of the newest classes of antibiotics. They inhibit bacterial growth by interfering with protein synthesis. The mechanism of oxazolidinone action and the precise location of the drug binding site in the ribosome are unknown. We used a panel of photoreactive derivatives to identify the site of action of oxazolidinones in the ribosomes of bacterial and human cells. The in vivo crosslinking data were used to model the position of the oxazolidinone molecule within its binding site in the peptidyl transferase center (PTC). Oxazolidinones interact with the A site of the bacterial ribosome where they should interfere with the placement of the aminoacyl-tRNA. In human cells, oxazolidinones were crosslinked to rRNA in the PTC of mitochondrial, but not cytoplasmic, ribosomes. Interaction of oxazolidinones with the mitochondrial ribosomes provides a structural basis for the inhibition of mitochondrial protein synthesis, which is linked to clinical side effects associated with oxazolidinone therapy.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Tedizolid 23S ribosomal RNA Nucleotide Enteric bacteria and other eubacteria YesInhibitorDetails Tedizolid phosphate 23S ribosomal RNA Nucleotide Enteric bacteria and other eubacteria YesInhibitorDetails