Nature Chemical Biology, volume 13, issue 10, pages 1129-1136

Klebsazolicin inhibits 70S ribosome by obstructing the peptide exit tunnel

Metelev Mikhail ^{1, 2, 3, 4}

Osterman Ilya A. ^{3, 5}

Ghilarov Dmitry ^{3, 4}

Khabibullina Nelli F ⁶

Yakimov Alexander ^{2, 7}

Shabalin Konstantin ⁷

Utkina Irina ^{2, 3}

Travin Dmitry Y ⁸

Komarova Ekaterina S. ^{3, 8}

Serebryakova Marina ^{4, 5}

Artamonova Tatyana ²

Khodorkovskii Mikhail ²

Konevega Andrey L. ^{2, 7}

Sergiev Petr V. ^{3, 5}

Severinov Konstantin ^{2, 3, 4, 9}

Polikanov Yury S ^{6, 10}

Hide authors affiliations Show authors affiliations: 10 affiliations

Institute of Antimicrobial Chemotherapy, Smolensk State Medical Academy, Smolensk, Russia |

Research Center of Nanobiotechnologies, Peter the Great St.Petersburg Polytechnic University, St. Petersburg, Russia |

Center for Data-Intensive Biomedicine and Biotechnology, Skolkovo Institute of Science and Technology, Moscow, Russia |

⁴

Institute of Gene Biology of the Russian Academy of Sciences, Moscow, Russia |

⁵

Department of Chemistry and A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia |

⁶

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

⁷

Petersburg Nuclear Physics Institute, NRC Kurchatov Institute, Gatchina, Russia

National Research Centre "Kurchatov Institute"

Petersburg Nuclear Physics Institute of NRC «Kurchatov Institute»

⁸

Department of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia |

⁹

Waksman Institute for Microbiology, Rutgers, The State University of New Jersey, Piscataway, USA |

¹⁰

Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, USA |

Publication type: Journal Article

Publication date: 2017-08-28

Springer Nature

Journal: Nature Chemical Biology

Quartile SCImago

Quartile WOS

Impact factor: 14.8

ISSN: 15524450, 15524469

DOI: 10.1038/nchembio.2462

Copy DOI

PubMed ID: 28846667

Molecular Biology

Cell Biology

Abstract

While screening of small-molecular metabolites produced by most cultivatable microorganisms often results in rediscovery of known compounds, genome-mining programs allow to harness much greater chemical diversity and result in discovery of new molecular scaffolds. Here we report genome-guided identification of a new antibiotic klebsazolicin (KLB) from Klebsiella pneumoniae that inhibits growth of sensitive cells by targeting ribosome. A member of ribosomally-synthesized post-translationally modified peptides (RiPPs), KLB is characterized by the presence of unique N-terminal amidine ring essential for its activity. Biochemical in vitro studies indicate that KLB inhibits ribosome by interfering with translation elongation. Structural analysis of the ribosome-KLB complex reveals the compound bound in the peptide exit tunnel overlapping with the binding sites of macrolides or streptogramins-B. KLB adopts compact conformation and largely obstructs the tunnel. Engineered KLB fragments retain in vitro activity and can serve as a starting point for the development of new bioactive compounds.

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Citations by journals

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Frontiers in Microbiology	Frontiers in Microbiology, 4, 9.3% Frontiers in Microbiology 4 publications, 9.3%
Journal of the American Chemical Society	Journal of the American Chemical Society, 3, 6.98% Journal of the American Chemical Society 3 publications, 6.98%
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Microbiology	Microbiology, 1, 2.33% Microbiology 1 publication, 2.33%
Frontiers in Molecular Biosciences	Frontiers in Molecular Biosciences, 1, 2.33% Frontiers in Molecular Biosciences 1 publication, 2.33%
Frontiers in Genetics	Frontiers in Genetics, 1, 2.33% Frontiers in Genetics 1 publication, 2.33%
Nature Chemistry	Nature Chemistry, 1, 2.33% Nature Chemistry 1 publication, 2.33%
Nature Reviews Chemistry	Nature Reviews Chemistry, 1, 2.33% Nature Reviews Chemistry 1 publication, 2.33%
Applied Microbiology and Biotechnology	Applied Microbiology and Biotechnology, 1, 2.33% Applied Microbiology and Biotechnology 1 publication, 2.33%
Journal of Molecular Biology	Journal of Molecular Biology, 1, 2.33% Journal of Molecular Biology 1 publication, 2.33%
Structure	Structure, 1, 2.33% Structure 1 publication, 2.33%
Biopolymers	Biopolymers, 1, 2.33% Biopolymers 1 publication, 2.33%
Biochemistry	Biochemistry, 1, 2.33% Biochemistry 1 publication, 2.33%
Chemical Reviews	Chemical Reviews, 1, 2.33% Chemical Reviews 1 publication, 2.33%
Chemical Science	Chemical Science, 1, 2.33% Chemical Science 1 publication, 2.33%
FEMS Microbiology Reviews	FEMS Microbiology Reviews, 1, 2.33% FEMS Microbiology Reviews 1 publication, 2.33%
Journal of Industrial Microbiology and Biotechnology	Journal of Industrial Microbiology and Biotechnology, 1, 2.33% Journal of Industrial Microbiology and Biotechnology 1 publication, 2.33%
Briefings in Bioinformatics	Briefings in Bioinformatics, 1, 2.33% Briefings in Bioinformatics 1 publication, 2.33%
Science advances	Science advances, 1, 2.33% Science advances 1 publication, 2.33%
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Annual Review of Biochemistry	Annual Review of Biochemistry, 1, 2.33% Annual Review of Biochemistry 1 publication, 2.33%
RNA	RNA, 1, 2.33% RNA 1 publication, 2.33%
ACS Bio & Med Chem Au	ACS Bio & Med Chem Au, 1, 2.33% ACS Bio & Med Chem Au 1 publication, 2.33%
RSC Medicinal Chemistry	RSC Medicinal Chemistry, 1, 2.33% RSC Medicinal Chemistry 1 publication, 2.33%
Marine Drugs	Marine Drugs, 1, 2.33% Marine Drugs 1 publication, 2.33%
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Citations by publishers

	1 2 3 4 5 6 7 8
Springer Nature	Springer Nature, 8, 18.6% Springer Nature 8 publications, 18.6%
American Chemical Society (ACS)	American Chemical Society (ACS), 6, 13.95% American Chemical Society (ACS) 6 publications, 13.95%
Frontiers Media S.A.	Frontiers Media S.A., 6, 13.95% Frontiers Media S.A. 6 publications, 13.95%
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 3, 6.98% Multidisciplinary Digital Publishing Institute (MDPI) 3 publications, 6.98%
Elsevier	Elsevier, 2, 4.65% Elsevier 2 publications, 4.65%
Royal Society of Chemistry (RSC)	Royal Society of Chemistry (RSC), 2, 4.65% Royal Society of Chemistry (RSC) 2 publications, 4.65%
Oxford University Press	Oxford University Press, 2, 4.65% Oxford University Press 2 publications, 4.65%
Acta Naturae Ltd	Acta Naturae Ltd, 1, 2.33% Acta Naturae Ltd 1 publication, 2.33%
American Society for Microbiology	American Society for Microbiology, 1, 2.33% American Society for Microbiology 1 publication, 2.33%
Microbiology Society	Microbiology Society, 1, 2.33% Microbiology Society 1 publication, 2.33%
Wiley	Wiley, 1, 2.33% Wiley 1 publication, 2.33%
American Association for the Advancement of Science (AAAS)	American Association for the Advancement of Science (AAAS), 1, 2.33% American Association for the Advancement of Science (AAAS) 1 publication, 2.33%
Oles Honchar Dnipropetrovsk National University	Oles Honchar Dnipropetrovsk National University, 1, 2.33% Oles Honchar Dnipropetrovsk National University 1 publication, 2.33%
Annual Reviews	Annual Reviews, 1, 2.33% Annual Reviews 1 publication, 2.33%
Cold Spring Harbor Laboratory	Cold Spring Harbor Laboratory, 1, 2.33% Cold Spring Harbor Laboratory 1 publication, 2.33%
	1 2 3 4 5 6 7 8

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GOST Copy

Metelev M. et al. Klebsazolicin inhibits 70S ribosome by obstructing the peptide exit tunnel // Nature Chemical Biology. 2017. Vol. 13. No. 10. pp. 1129-1136.

GOST all authors (up to 50) Copy

Metelev M., Osterman I. A., Ghilarov D., Khabibullina N. F., Yakimov A., Shabalin K., Utkina I., Travin D. Y., Komarova E. S., Serebryakova M., Artamonova T., Khodorkovskii M., Konevega A. L., Sergiev P. V., Severinov K., Polikanov Y. S. Klebsazolicin inhibits 70S ribosome by obstructing the peptide exit tunnel // Nature Chemical Biology. 2017. Vol. 13. No. 10. pp. 1129-1136.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1038/nchembio.2462

UR - https://doi.org/10.1038%2Fnchembio.2462

TI - Klebsazolicin inhibits 70S ribosome by obstructing the peptide exit tunnel

T2 - Nature Chemical Biology

AU - Metelev, Mikhail

AU - Osterman, Ilya A.

AU - Khabibullina, Nelli F

AU - Yakimov, Alexander

AU - Shabalin, Konstantin

AU - Utkina, Irina

AU - Travin, Dmitry Y

AU - Komarova, Ekaterina S.

AU - Serebryakova, Marina

AU - Artamonova, Tatyana

AU - Khodorkovskii, Mikhail

AU - Konevega, Andrey L.

AU - Sergiev, Petr V.

AU - Polikanov, Yury S

AU - Ghilarov, Dmitry

AU - Severinov, Konstantin

PY - 2017

DA - 2017/08/28 00:00:00

PB - Springer Nature

SP - 1129-1136

IS - 10

VL - 13

PMID - 28846667

SN - 1552-4450

SN - 1552-4469

ER -

BibTex |

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BibTex Copy

@article{2017_Metelev,

author = {Mikhail Metelev and Ilya A. Osterman and Nelli F Khabibullina and Alexander Yakimov and Konstantin Shabalin and Irina Utkina and Dmitry Y Travin and Ekaterina S. Komarova and Marina Serebryakova and Tatyana Artamonova and Mikhail Khodorkovskii and Andrey L. Konevega and Petr V. Sergiev and Yury S Polikanov and Dmitry Ghilarov and Konstantin Severinov},

title = {Klebsazolicin inhibits 70S ribosome by obstructing the peptide exit tunnel},

journal = {Nature Chemical Biology},

year = {2017},

volume = {13},

publisher = {Springer Nature},

month = {aug},

url = {https://doi.org/10.1038%2Fnchembio.2462},

number = {10},

pages = {1129--1136},

doi = {10.1038/nchembio.2462}

}

MLA

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MLA Copy

Metelev, Mikhail, et al. “Klebsazolicin inhibits 70S ribosome by obstructing the peptide exit tunnel.” Nature Chemical Biology, vol. 13, no. 10, Aug. 2017, pp. 1129-1136. https://doi.org/10.1038%2Fnchembio.2462.

Found error?

Publisher

Springer Nature

Journal

Nature Chemical Biology

Quartile SCImago

Quartile WOS

Impact factor

14.8

ISSN

15524450 (Print)
15524469 (Electronic)

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