EMD-12575

Single-particle
3.1 Å
EMD-12575 Deposition: 08/03/2021
Map released: 14/07/2021
Last modified: 11/08/2021
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
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EMD-12575

Structure of ErmDL-Telithromycin-stalled 70S E. coli ribosomal complex with A and P-tRNA

EMD-12575

Single-particle
3.1 Å
EMD-12575 Deposition: 08/03/2021
Map released: 14/07/2021
Last modified: 11/08/2021
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Escherichia coli
Sample: Structure of ErmDL-Erythromycin-stalled 70S E. coli ribosomal complex with P-tRNA
Fitted models: 7nsq (Avg. Q-score: 0.52)

Deposition Authors: Beckert B, Wilson DN
Structural and mechanistic basis for translation inhibition by macrolide and ketolide antibiotics.
PUBMED: 34294725
DOI: doi:10.1038/s41467-021-24674-9
ISSN: 2041-1723
Abstract:
Macrolides and ketolides comprise a family of clinically important antibiotics that inhibit protein synthesis by binding within the exit tunnel of the bacterial ribosome. While these antibiotics are known to interrupt translation at specific sequence motifs, with ketolides predominantly stalling at Arg/Lys-X-Arg/Lys motifs and macrolides displaying a broader specificity, a structural basis for their context-specific action has been lacking. Here, we present structures of ribosomes arrested during the synthesis of an Arg-Leu-Arg sequence by the macrolide erythromycin (ERY) and the ketolide telithromycin (TEL). Together with deep mutagenesis and molecular dynamics simulations, the structures reveal how ERY and TEL interplay with the Arg-Leu-Arg motif to induce translational arrest and illuminate the basis for the less stringent sequence-specific action of ERY over TEL. Because programmed stalling at the Arg/Lys-X-Arg/Lys motifs is used to activate expression of antibiotic resistance genes, our study also provides important insights for future development of improved macrolide antibiotics.