Structural conservation of antibiotic interaction with ribosomes.
Journal
Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
22
02
2023
accepted:
26
06
2023
medline:
14
9
2023
pubmed:
8
8
2023
entrez:
7
8
2023
Statut:
ppublish
Résumé
The ribosome is a major target for clinically used antibiotics, but multidrug resistant pathogenic bacteria are making our current arsenal of antimicrobials obsolete. Here we present cryo-electron-microscopy structures of 17 distinct compounds from six different antibiotic classes bound to the bacterial ribosome at resolutions ranging from 1.6 to 2.2 Å. The improved resolution enables a precise description of antibiotic-ribosome interactions, encompassing solvent networks that mediate multiple additional interactions between the drugs and their target. Our results reveal a high structural conservation in the binding mode between antibiotics with the same scaffold, including ordered water molecules. Water molecules are visualized within the antibiotic binding sites that are preordered, become ordered in the presence of the drug and that are physically displaced on drug binding. Insight into RNA-ligand interactions will facilitate development of new antimicrobial agents, as well as other RNA-targeting therapies.
Identifiants
pubmed: 37550453
doi: 10.1038/s41594-023-01047-y
pii: 10.1038/s41594-023-01047-y
pmc: PMC10497419
doi:
Substances chimiques
Anti-Bacterial Agents
0
RNA
63231-63-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1380-1392Informations de copyright
© 2023. The Author(s).
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