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RNA, том 26, издание 6, номера страниц: 715-723

Insights into the improved macrolide inhibitory activity from the high-resolution cryo-EM structure of dirithromycin bound to the E. coli 70S ribosome

Тип документаJournal Article
Дата публикации2020-06-01
ИздательCold Spring Harbor Laboratory Press
Название журналаRNA
Квартиль по SCImagoQ1
Квартиль по Web of ScienceQ2
Импакт-фактор 20215.64
ISSN13558382, 14699001
Molecular Biology
Краткое описание

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 Thermus thermophilus 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 Escherichia coli 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.

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1. Pichkur E.B. и др. Insights into the improved macrolide inhibitory activity from the high-resolution cryo-EM structure of dirithromycin bound to the E. coli 70S ribosome // RNA. 2020. Т. 26. № 6. С. 715–723.


DO - 10.1261/rna.073817.119

UR -

TI - Insights into the improved macrolide inhibitory activity from the high-resolution cryo-EM structure of dirithromycin bound to the E. coli 70S ribosome

T2 - RNA

AU - Pichkur, Evgeny B.

AU - Paleskava, Alena

AU - Tereshchenkov, Andrey G.

AU - Kasatsky, Pavel

AU - Komarova, Ekaterina S.

AU - Shiriaev, Dmitrii I.

AU - Bogdanov, Alexey A.

AU - Dontsova, Olga A.

AU - Osterman, Ilya A.

AU - Sergiev, Petr V.

AU - Polikanov, Yury S.

AU - Myasnikov, Alexander G.

AU - Konevega, Andrey L.

PY - 2020

DA - 2020/03/06

PB - Cold Spring Harbor Laboratory

SP - 715-723

IS - 6

VL - 26

SN - 1355-8382

SN - 1469-9001

ER -

BibTex |


doi = {10.1261/rna.073817.119},

url = {},

year = 2020,

month = {mar},

publisher = {Cold Spring Harbor Laboratory},

volume = {26},

number = {6},

pages = {715--723},

author = {Evgeny B. Pichkur and Alena Paleskava and Andrey G. Tereshchenkov and Pavel Kasatsky and Ekaterina S. Komarova and Dmitrii I. Shiriaev and Alexey A. Bogdanov and Olga A. Dontsova and Ilya A. Osterman and Petr V. Sergiev and Yury S. Polikanov and Alexander G. Myasnikov and Andrey L. Konevega},

title = {Insights into the improved macrolide inhibitory activity from the high-resolution cryo-{EM} structure of dirithromycin bound to the E. coli 70S ribosome}


Pichkur, Evgeny B. et al. “Insights into the Improved Macrolide Inhibitory Activity from the High-Resolution Cryo-EM Structure of Dirithromycin Bound to the E. Coli 70S Ribosome.” RNA 26.6 (2020): 715–723. Crossref. Web.