The macrolide binding site on the bacterial ribosome.
Macrolides are a diverse group of antimicrobials that are widely prescribed in clinical and veterinary medicine. Macrolides inhibit bacterial growth by interacting with the large (50S) subunit of the ribosome and thereby blocking protein synthesis. The liberal application of macrolides and the mechanistically similar lincosamide and streptogramin B compounds has in recent years led to increased prevalence of resistance to these drugs. To counteract this trend and improve the efficacy of treatment, numerous macrolide derivatives have been developed and the latest of these, the ketolides, are now becoming available for clinical use. However, in the on-going battle against resistance pathogens continual improvement of drugs will be necessary, and more efficient means of drug development are required. An indication of how rational drug design might be feasible is offered by the recent crystallographic structures of the bacterial ribosome. These structures give us a view of the macrolide target at previously unseen resolution, enabling us to understand the molecular details of macrolide interaction and resistance, and provide strong clues about potential new drug targets.
Poehlsgaard
Jacob
J
Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark.
Douthwaite
Stephen
S
D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001419:Bacteria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D001665:Binding Sites; D004351:Drug Resistance; D006801:Humans; D018942:Macrolides; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D012270:Ribosomes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
D000900:Anti-Bacterial Agents; D018942:Macrolides