Nature Chemical Biology, издание 16, том 10, номера страниц: 1071-1077

Tetracenomycin X inhibits translation by binding within the ribosomal exit tunnel

Osterman Ilya A 1, 2
, 
Wieland Maximiliane 3
, 
Maviza Tinashe P 2
, 
Lashkevich Kseniya A 1
, 
Lukianov Dmitrii A. 2
, 
Komarova Ekaterina S 1, 2
, 
Zakalyukina Yuliya V 4
, 
Buschauer Robert 5
, 
Shiriaev Dmitrii I 1
, 
Leyn Semen A. 6, 7
, 
Zlamal Jaime E 7
, 
Biryukov Mikhail V 4
, 
Skvortsov Dmitry A. 1
, 
Tashlitsky Vadim N. 1
, 
Polshakov Vladimir I. 8
, 
Cheng Jingdong 5
, 
Polikanov Yury S 9
, 
Bogdanov Alexey A. 1
, 
Osterman Andrei L. 7
, 
Dmitriev Sergey E. 1
, 
Beckmann Roland 5
, 
Dontsova Olga A. 1, 2, 10
, 
Wilson Daniel W. 3
, 
Sergiev Petr V. 1, 2
1
 
2
 
3
 
Institute for Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany
4
 
5
 
Gene Center, Department of Biochemistry, University of Munich, Munich, Germany
6
 
7
 
Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, USA
8
 
9
 
Department of Biological Sciences, University of Illinois at Chicago, Chicago, USA
10
 
Тип публикации: Journal Article
Дата публикации: 2020-06-29
Springer Nature
Springer Nature
Журнал:  Nature Chemical Biology
Квартиль SCImago: Q1
Квартиль WOS: Q1
Impact factor: 14.8
ISSN: 15524450, 15524469
Molecular Biology
Cell Biology
Краткое описание
The increase in multi-drug resistant pathogenic bacteria is making our current arsenal of clinically used antibiotics obsolete, highlighting the urgent need for new lead compounds with distinct target binding sites to avoid cross-resistance. Here we report that the aromatic polyketide antibiotic tetracenomycin (TcmX) is a potent inhibitor of protein synthesis, and does not induce DNA damage as previously thought. Despite the structural similarity to the well-known translation inhibitor tetracycline, we show that TcmX does not interact with the small ribosomal subunit, but rather binds to the large subunit, within the polypeptide exit tunnel. This previously unappreciated binding site is located adjacent to the macrolide-binding site, where TcmX stacks on the noncanonical basepair formed by U1782 and U2586 of the 23S ribosomal RNA. Although the binding site is distinct from the macrolide antibiotics, our results indicate that like macrolides, TcmX allows translation of short oligopeptides before further translation is blocked. Structural and biochemical analysis reveal that tetracenomycin X acts as an inhibitor of protein synthesis by binding within the exit tunnel in a large ribosomal unit to prevent the prolongation of the nascent polypeptide chain.
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1. Osterman I.A. и др. Tetracenomycin X inhibits translation by binding within the ribosomal exit tunnel // Nature Chemical Biology. 2020. Т. 16. № 10. С. 1071–1077.
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TY - JOUR

DO - 10.1038/s41589-020-0578-x

UR - http://dx.doi.org/10.1038/s41589-020-0578-x

TI - Tetracenomycin X inhibits translation by binding within the ribosomal exit tunnel

T2 - Nature Chemical Biology

AU - Osterman, Ilya A.

AU - Wieland, Maximiliane

AU - Maviza, Tinashe P.

AU - Lashkevich, Kseniya A.

AU - Lukianov, Dmitrii A.

AU - Komarova, Ekaterina S.

AU - Zakalyukina, Yuliya V.

AU - Buschauer, Robert

AU - Shiriaev, Dmitrii I.

AU - Leyn, Semen A.

AU - Zlamal, Jaime E.

AU - Biryukov, Mikhail V.

AU - Skvortsov, Dmitry A.

AU - Tashlitsky, Vadim N.

AU - Polshakov, Vladimir I.

AU - Cheng, Jingdong

AU - Polikanov, Yury S.

AU - Bogdanov, Alexey A.

AU - Osterman, Andrei L.

AU - Dmitriev, Sergey E.

AU - Beckmann, Roland

AU - Dontsova, Olga A.

AU - Wilson, Daniel N.

AU - Sergiev, Petr V.

PY - 2020

DA - 2020/06/29

PB - Springer Science and Business Media LLC

SP - 1071-1077

IS - 10

VL - 16

SN - 1552-4450

SN - 1552-4469

ER -

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@article{2020,

doi = {10.1038/s41589-020-0578-x},

url = {https://doi.org/10.1038%2Fs41589-020-0578-x},

year = 2020,

month = {jun},

publisher = {Springer Science and Business Media {LLC}},

volume = {16},

number = {10},

pages = {1071--1077},

author = {Ilya A. Osterman and Maximiliane Wieland and Tinashe P. Maviza and Kseniya A. Lashkevich and Dmitrii A. Lukianov and Ekaterina S. Komarova and Yuliya V. Zakalyukina and Robert Buschauer and Dmitrii I. Shiriaev and Semen A. Leyn and Jaime E. Zlamal and Mikhail V. Biryukov and Dmitry A. Skvortsov and Vadim N. Tashlitsky and Vladimir I. Polshakov and Jingdong Cheng and Yury S. Polikanov and Alexey A. Bogdanov and Andrei L. Osterman and Sergey E. Dmitriev and Roland Beckmann and Olga A. Dontsova and Daniel N. Wilson and Petr V. Sergiev},

title = {Tetracenomycin X inhibits translation by binding within the ribosomal exit tunnel}

}

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Osterman, Ilya A. et al. “Tetracenomycin X Inhibits Translation by Binding Within the Ribosomal Exit Tunnel.” Nature Chemical Biology 16.10 (2020): 1071–1077. Crossref. Web.