Open Access
RNA, volume 26, issue 6, pages 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
Pichkur Evgeny B
1
,
Dontsova Olga A.
2, 3, 4
,
Sergiev Petr V.
,
Osterman Ilya A.
,
Paleskava Alena
5, 6
,
Konevega Andrey L.
5, 6, 7
,
Tereshchenkov Andrey G
8, 9, 10
,
Shiriaev Dmitrii I
8, 9, 10
,
Polikanov Yury S
11
,
Kasatsky Pavel
,
Myasnikov Alexander G.
,
Kasatsky Pavel
1
,
Komarova Ekaterina S
12
,
Bogdanov Alexey A.
8, 9, 10
,
Osterman Ilya A
3, 4
,
Sergiev Petr V.
3, 4
,
Myasnikov Alexander G.
6, 13, 14
1
6
8
Moscow 119992 Russia
|
11
Departments of Biological Sciences and Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
|
13
10Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA
|
Publication type: Journal Article
Publication date: 2020-03-06
PubMed ID:
32144191
Molecular Biology
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 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.
Citations by journals
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Journal of Medicinal Chemistry
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2 publications, 13.33%
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2 publications, 13.33%
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1 publication, 6.67%
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1 publication, 6.67%
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1 publication, 6.67%
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Proceedings of the National Academy of Sciences of the United States of America
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1 publication, 6.67%
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eLife
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eLife
1 publication, 6.67%
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Nature Communications
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1 publication, 6.67%
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Cell
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1 publication, 6.67%
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1 publication, 6.67%
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1
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Citations by publishers
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1
2
3
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Multidisciplinary Digital Publishing Institute (MDPI)
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3 publications, 20%
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Springer Nature
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3 publications, 20%
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American Chemical Society (ACS)
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2 publications, 13.33%
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Proceedings of the National Academy of Sciences (PNAS)
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Proceedings of the National Academy of Sciences (PNAS)
1 publication, 6.67%
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eLife Sciences Publications
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eLife Sciences Publications
1 publication, 6.67%
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Elsevier
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Elsevier
1 publication, 6.67%
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Frontiers Media S.A.
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Frontiers Media S.A.
1 publication, 6.67%
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1
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3
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Pichkur E. 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. 2020. Vol. 26. No. 6. pp. 715-723.
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Paleskava A., Konevega A. L., Myasnikov A. G., Polikanov Y. S., Sergiev P. V., Osterman I. A., Dontsova O. A., Bogdanov A. A., Shiriaev D. I., Komarova E. S., Kasatsky P., Tereshchenkov A. G., Pichkur E. B., Kasatsky P., Komarova E. S., Bogdanov A. A., Osterman I. A., Sergiev P. V., Myasnikov A. G. 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. Vol. 26. No. 6. pp. 715-723.
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TY - JOUR
DO - 10.1261/rna.073817.119
UR - https://doi.org/10.1261%2Frna.073817.119
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.
AU - Kasatsky, Pavel
AU - Komarova, Ekaterina S
AU - Bogdanov, Alexey A.
AU - Osterman, Ilya A
AU - Sergiev, Petr V.
AU - Myasnikov, Alexander G.
PY - 2020
DA - 2020/03/06 00:00:00
PB - Cold Spring Harbor Laboratory
SP - 715-723
IS - 6
VL - 26
PMID - 32144191
SN - 1355-8382
SN - 1469-9001
ER -
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@article{2020_Pichkur,
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 and Pavel Kasatsky and Ekaterina S Komarova and Alexey A. Bogdanov and Ilya A Osterman and Petr V. Sergiev and Alexander G. Myasnikov},
title = {Insights into the improved macrolide inhibitory activity from the high-resolution cryo-EM structure of dirithromycin bound to the E. coli 70S ribosome},
journal = {RNA},
year = {2020},
volume = {26},
publisher = {Cold Spring Harbor Laboratory},
month = {mar},
url = {https://doi.org/10.1261%2Frna.073817.119},
number = {6},
pages = {715--723},
doi = {10.1261/rna.073817.119}
}
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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, vol. 26, no. 6, Mar. 2020, pp. 715-723. https://doi.org/10.1261%2Frna.073817.119.