6XZB

E. coli 70S ribosome in complex with dirithromycin, fMet-Phe-tRNA(Phe) and deacylated tRNA(iMet) (focused classification).

This is a non-PDB format compatible entry.

Summary for 6XZB

• Entry DOI: 10.2210/pdb6xzb/pdb
• EMDB information: 10657
• Descriptor: 16S rRNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (55 entities in total)
• Functional Keywords: 70s ribosome, dirithromycin, antibiotics, cryo-em, ribosome
• Biological source: Escherichia coli K-12; More
• Total number of polymer chains: 54
• Total formula weight: 2164911.72

Authors

Pichkur, E.B.,Polikanov, Y.S.,Myasnikov, A.G.,Konevega, A.L. (deposition date: 2020-02-03, release date: 2020-11-04, Last modification date: 2025-03-12)

Primary citation

Pichkur, E.B.,Paleskava, A.,Tereshchenkov, A.G.,Kasatsky, P.,Komarova, E.S.,Shiriaev, D.I.,Bogdanov, A.A.,Dontsova, O.A.,Osterman, I.A.,Sergiev, P.V.,Polikanov, Y.S.,Myasnikov, A.G.,Konevega, A.L.
Insights into the improved macrolide inhibitory activity from the high-resolution cryo-EM structure of dirithromycin bound to the E. coli 70S ribosome.
Rna, 26:715-723, 2020

PubMed Abstract: Macrolides are one of the most successful and widely used classes of antibacterials, which kill or stop the growth of pathogenic bacteria by binding near the active site of the ribosome and interfering with protein synthesis. Dirithromycin is a derivative of the prototype macrolide erythromycin with additional hydrophobic side chain. In our recent study, we have discovered that the side chain of dirithromycin forms lone pair-π stacking interaction with the aromatic imidazole ring of the His69 residue in ribosomal protein uL4 of the 70S ribosome. In the current work, we found that neither the presence of the side chain, nor the additional contact with the ribosome, improve the binding affinity of dirithromycin to the ribosome. Nevertheless, we found that dirithromycin is a more potent inhibitor of in vitro protein synthesis in comparison with its parent compound, erythromycin. Using high-resolution cryo-electron microscopy, we determined the structure of the dirithromycin bound to the translating 70S ribosome, which suggests that the better inhibitory properties of the drug could be rationalized by the side chain of dirithromycin pointing into the lumen of the nascent peptide exit tunnel, where it can interfere with the normal passage of the growing polypeptide chain.

PubMed: 32144191
DOI: 10.1261/rna.073817.119

Experimental method

ELECTRON MICROSCOPY (2.54 Å)