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Proceedings of the National Academy of Sciences of the United States of America, volume 113, issue 27, pages 7527-7532

Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome

Arenz Stefan 1
Juette Manuel F 2
Gräf Michael 1
Nguyen Fabian 1
Huter Paul 1
Polikanov Yury S. 3, 4
Blanchard Scott C 2
Wilson Daniel N. 1, 5
1
 
Gene Center and Department for Biochemistry, University of Munich, 81377 Munich, Germany;
3
 
Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607;
4
 
Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60607;
5
 
Center for integrated Protein Science Munich, University of Munich, 81377 Munich, Germany
Publication typeJournal Article
Publication date2016-06-21
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor11.1
ISSN00278424, 10916490
Multidisciplinary
Abstract
Significance

The ribosome is the protein-synthesizing machine of the cell and is a major target for antibiotics. The increase in multidrug-resistant bacteria has limited the utility of our current arsenal of clinically used antibiotics, highlighting the need for further development of compounds that have distinct binding sites and do not display cross-resistance. Using cryo-electron microscopy, we have visualized the binding site of the orthosomycins evernimicin and avilamycin on the bacterial 70S ribosome. The binding site and mode of interaction of evernimicin and avilamycin are distinct from other ribosome-targeting antibiotics. Together with single-molecule studies, our structures reveal how the orthosomycin antibiotics inhibit protein synthesis by preventing accommodation of the aminoacyl-tRNA at the A site of the ribosome.

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GOST Copy
Arenz S. et al. Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome // Proceedings of the National Academy of Sciences of the United States of America. 2016. Vol. 113. No. 27. pp. 7527-7532.
GOST all authors (up to 50) Copy
Arenz S., Juette M. F., Gräf M., Nguyen F., Huter P., Polikanov Y. S., Blanchard S. C., Wilson D. N. Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome // Proceedings of the National Academy of Sciences of the United States of America. 2016. Vol. 113. No. 27. pp. 7527-7532.
RIS |
Cite this
RIS Copy
TY - JOUR
DO - 10.1073/pnas.1604790113
UR - https://doi.org/10.1073%2Fpnas.1604790113
TI - Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome
T2 - Proceedings of the National Academy of Sciences of the United States of America
AU - Arenz, Stefan
AU - Juette, Manuel F
AU - Gräf, Michael
AU - Nguyen, Fabian
AU - Huter, Paul
AU - Polikanov, Yury S.
AU - Blanchard, Scott C
AU - Wilson, Daniel N.
PY - 2016
DA - 2016/06/21 00:00:00
PB - Proceedings of the National Academy of Sciences (PNAS)
SP - 7527-7532
IS - 27
VL - 113
PMID - 27330110
SN - 0027-8424
SN - 1091-6490
ER -
BibTex |
Cite this
BibTex Copy
@article{2016_Arenz
author = {Stefan Arenz and Manuel F Juette and Michael Gräf and Fabian Nguyen and Paul Huter and Yury S. Polikanov and Scott C Blanchard and Daniel N. Wilson},
title = {Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2016},
volume = {113},
publisher = {Proceedings of the National Academy of Sciences (PNAS)},
month = {jun},
url = {https://doi.org/10.1073%2Fpnas.1604790113},
number = {27},
pages = {7527--7532},
doi = {10.1073/pnas.1604790113}
}
MLA
Cite this
MLA Copy
Arenz, Stefan, et al. “Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome.” Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 27, Jun. 2016, pp. 7527-7532. https://doi.org/10.1073%2Fpnas.1604790113.
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