Structural Conservation of Antibiotic Interaction with Ribosomes

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2023 Aug 7

PMID 37550453

Authors

Helge Paternoga

Caillan Crowe-McAuliffe

Lars V Bock

Timm O Koller

Martino Morici

Bertrand Beckert

Alexander G Myasnikov

Helmut Grubmuller

Jiri Novacek

Daniel N Wilson

Affiliations

Soon will be listed here.

Abstract

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.

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