7NSP

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

This is a non-PDB format compatible entry.

Summary for 7NSP

• Entry DOI: 10.2210/pdb7nsp/pdb
• EMDB information: 12574
• Descriptor: 23S rRNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (57 entities in total)
• Functional Keywords: antibiotic, ermdl, erythromycin, macrolide, stalling, ribosome
• Biological source: Escherichia coli; More
• Total number of polymer chains: 56
• Total formula weight: 2169451.87

Authors

Beckert, B.,Wilson, D.N. (deposition date: 2021-03-08, release date: 2021-08-11, Last modification date: 2024-10-16)

Primary citation

Beckert, B.,Leroy, E.C.,Sothiselvam, S.,Bock, L.V.,Svetlov, M.S.,Graf, M.,Arenz, S.,Abdelshahid, M.,Seip, B.,Grubmuller, H.,Mankin, A.S.,Innis, C.A.,Vazquez-Laslop, N.,Wilson, D.N.
Structural and mechanistic basis for translation inhibition by macrolide and ketolide antibiotics.
Nat Commun, 12:4466-4466, 2021

PubMed 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.

PubMed: 34294725
DOI: 10.1038/s41467-021-24674-9

Experimental method

ELECTRON MICROSCOPY (3.5 Å)