Nature Chemical Biology, volume 16, issue 10, pages 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}

Hide authors affiliations Show authors affiliations: 10 affiliations

Department of Chemistry, Faculty of Bioengineering and Bioinformatics and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia |

Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo, Russia |

Institute for Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany |

⁴

Department of Soil Science and Department of Biology, Lomonosov Moscow State University, Moscow, Russia |

⁵

Gene Center, Department of Biochemistry, University of Munich, Munich, Germany |

⁶

A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow, Russia |

⁷

Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, USA |

⁸

Center for Magnetic Tomography and Spectroscopy, Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow, Russia |

⁹

Department of Biological Sciences, University of Illinois at Chicago, Chicago, USA |

¹⁰

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia |

Publication type: Journal Article

Publication date: 2020-06-29

Springer Nature

Journal: Nature Chemical Biology

Quartile SCImago

Quartile WOS

Impact factor: 14.8

ISSN: 15524450, 15524469

DOI: 10.1038/s41589-020-0578-x

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Molecular Biology

Cell Biology

Abstract

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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Citations by journals

	1 2 3
Biochemistry (Moscow)	Biochemistry (Moscow), 3, 7.14% Biochemistry (Moscow) 3 publications, 7.14%
Microorganisms	Microorganisms, 3, 7.14% Microorganisms 3 publications, 7.14%
Nature Chemical Biology	Nature Chemical Biology, 3, 7.14% Nature Chemical Biology 3 publications, 7.14%
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Antibiotics	Antibiotics, 2, 4.76% Antibiotics 2 publications, 4.76%
Insects	Insects, 2, 4.76% Insects 2 publications, 4.76%
Nature Communications	Nature Communications, 2, 4.76% Nature Communications 2 publications, 4.76%
Antonie van Leeuwenhoek	Antonie van Leeuwenhoek, 1, 2.38% Antonie van Leeuwenhoek 1 publication, 2.38%
Acta Naturae	Acta Naturae, 1, 2.38% Acta Naturae 1 publication, 2.38%
Frontiers in Immunology	Frontiers in Immunology, 1, 2.38% Frontiers in Immunology 1 publication, 2.38%
Marine Drugs	Marine Drugs, 1, 2.38% Marine Drugs 1 publication, 2.38%
Cancers	Cancers, 1, 2.38% Cancers 1 publication, 2.38%
Frontiers in Microbiology	Frontiers in Microbiology, 1, 2.38% Frontiers in Microbiology 1 publication, 2.38%
Current Microbiology	Current Microbiology, 1, 2.38% Current Microbiology 1 publication, 2.38%
Current Opinion in Chemical Biology	Current Opinion in Chemical Biology, 1, 2.38% Current Opinion in Chemical Biology 1 publication, 2.38%
Life	Life, 1, 2.38% Life 1 publication, 2.38%
Biotechnology Journal	Biotechnology Journal, 1, 2.38% Biotechnology Journal 1 publication, 2.38%
Journal of Organic Chemistry	Journal of Organic Chemistry, 1, 2.38% Journal of Organic Chemistry 1 publication, 2.38%
Moscow University Biological Sciences Bulletin	Moscow University Biological Sciences Bulletin, 1, 2.38% Moscow University Biological Sciences Bulletin 1 publication, 2.38%
eLife	eLife, 1, 2.38% eLife 1 publication, 2.38%
ACS Omega	ACS Omega, 1, 2.38% ACS Omega 1 publication, 2.38%
RSC Medicinal Chemistry	RSC Medicinal Chemistry, 1, 2.38% RSC Medicinal Chemistry 1 publication, 2.38%
International Journal of Molecular Sciences	International Journal of Molecular Sciences, 1, 2.38% International Journal of Molecular Sciences 1 publication, 2.38%
Current Opinion in Microbiology	Current Opinion in Microbiology, 1, 2.38% Current Opinion in Microbiology 1 publication, 2.38%
Pharmaceuticals	Pharmaceuticals, 1, 2.38% Pharmaceuticals 1 publication, 2.38%
Journal of Natural Products	Journal of Natural Products, 1, 2.38% Journal of Natural Products 1 publication, 2.38%
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Citations by publishers

	2 4 6 8 10 12
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 12, 28.57% Multidisciplinary Digital Publishing Institute (MDPI) 12 publications, 28.57%
Springer Nature	Springer Nature, 7, 16.67% Springer Nature 7 publications, 16.67%
Pleiades Publishing	Pleiades Publishing, 4, 9.52% Pleiades Publishing 4 publications, 9.52%
Elsevier	Elsevier, 4, 9.52% Elsevier 4 publications, 9.52%
American Chemical Society (ACS)	American Chemical Society (ACS), 3, 7.14% American Chemical Society (ACS) 3 publications, 7.14%
Frontiers Media S.A.	Frontiers Media S.A., 2, 4.76% Frontiers Media S.A. 2 publications, 4.76%
Acta Naturae Ltd	Acta Naturae Ltd, 1, 2.38% Acta Naturae Ltd 1 publication, 2.38%
Wiley	Wiley, 1, 2.38% Wiley 1 publication, 2.38%
eLife Sciences Publications	eLife Sciences Publications, 1, 2.38% eLife Sciences Publications 1 publication, 2.38%
Royal Society of Chemistry (RSC)	Royal Society of Chemistry (RSC), 1, 2.38% Royal Society of Chemistry (RSC) 1 publication, 2.38%
	2 4 6 8 10 12

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Osterman I. A. et al. Tetracenomycin X inhibits translation by binding within the ribosomal exit tunnel // Nature Chemical Biology. 2020. Vol. 16. No. 10. pp. 1071-1077.

GOST all authors (up to 50) Copy

Osterman I. A., Wieland M., Maviza T. P., Lashkevich K. A., Lukianov D. A., Komarova E. S., Zakalyukina Y. V., Buschauer R., Shiriaev D. I., Leyn S. A., Zlamal J. E., Biryukov M. V., Skvortsov D. A., Tashlitsky V. N., Polshakov V. I., Cheng J., Polikanov Y. S., Bogdanov A. A., Osterman A. L., Dmitriev S. E., Beckmann R., Dontsova O. A., Wilson D. W., Sergiev P. V. Tetracenomycin X inhibits translation by binding within the ribosomal exit tunnel // Nature Chemical Biology. 2020. Vol. 16. No. 10. pp. 1071-1077.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1038/s41589-020-0578-x

UR - https://doi.org/10.1038%2Fs41589-020-0578-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 - 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 - Osterman, Andrei L.

AU - Dmitriev, Sergey E.

AU - Beckmann, Roland

AU - Dontsova, Olga A.

AU - Wilson, Daniel W.

AU - Sergiev, Petr V.

AU - Lukianov, Dmitrii A.

AU - Komarova, Ekaterina S

AU - Bogdanov, Alexey A.

PY - 2020

DA - 2020/06/29 00:00:00

PB - Springer Nature

SP - 1071-1077

IS - 10

VL - 16

SN - 1552-4450

SN - 1552-4469

ER -

BibTex |

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BibTex Copy

@article{2020_Osterman,

author = {Ilya A Osterman and Maximiliane Wieland and Tinashe P Maviza and Kseniya A Lashkevich 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 Andrei L. Osterman and Sergey E. Dmitriev and Roland Beckmann and Olga A. Dontsova and Daniel W. Wilson and Petr V. Sergiev and Dmitrii A. Lukianov and Ekaterina S Komarova and Alexey A. Bogdanov},

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

journal = {Nature Chemical Biology},

year = {2020},

volume = {16},

publisher = {Springer Nature},

month = {jun},

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

number = {10},

pages = {1071--1077},

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

}

MLA

Cite this

MLA Copy

Osterman, Ilya A., et al. “Tetracenomycin X inhibits translation by binding within the ribosomal exit tunnel.” Nature Chemical Biology, vol. 16, no. 10, Jun. 2020, pp. 1071-1077. https://doi.org/10.1038%2Fs41589-020-0578-x.

Found error?

Publisher

Springer Nature

Journal

Nature Chemical Biology

Quartile SCImago

Quartile WOS

Impact factor

14.8

ISSN

15524450 (Print)
15524469 (Electronic)

Labs

Laboratory of Nucleoprotein Chemistry, Department of Chemistry of Natural Compounds, Faculty of Chemistry

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