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Nucleic Acids Research, том 45, издание 12, номера страниц: 7507-7514

Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state

Khabibullina Nelli F.
Kasatsky Pavel
Kartsev Victor G.
Bogdanov Alexey A.
Konevega Andrey L.
Тип документаJournal Article
Дата публикации2017-05-13
ИздательOxford University Press
Название журналаNucleic Acids Research
Квартиль по SCImagoQ1
Квартиль по Web of ScienceQ1
Импакт-фактор 202119.16
ISSN03051048, 13624962
Краткое описание
Abstract The emergence of multi-drug resistant bacteria is limiting the effectiveness of commonly used antibiotics, which spurs a renewed interest in revisiting older and poorly studied drugs. Streptogramins A is a class of protein synthesis inhibitors that target the peptidyl transferase center (PTC) on the large subunit of the ribosome. In this work, we have revealed the mode of action of the PTC inhibitor madumycin II, an alanine-containing streptogramin A antibiotic, in the context of a functional 70S ribosome containing tRNA substrates. Madumycin II inhibits the ribosome prior to the first cycle of peptide bond formation. It allows binding of the tRNAs to the ribosomal A and P sites, but prevents correct positioning of their CCA-ends into the PTC thus making peptide bond formation impossible. We also revealed a previously unseen drug-induced rearrangement of nucleotides U2506 and U2585 of the 23S rRNA resulting in the formation of the U2506•G2583 wobble pair that was attributed to a catalytically inactive state of the PTC. The structural and biochemical data reported here expand our knowledge on the fundamental mechanisms by which peptidyl transferase inhibitors modulate the catalytic activity of the ribosome.
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1. Osterman I.A. и др. Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state // Nucleic Acids Research. 2017. Т. 45. № 12. С. 7507–7514.


DO - 10.1093/nar/gkx413

UR -

TI - Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state

T2 - Nucleic Acids Research

AU - Osterman, Ilya A.

AU - Khabibullina, Nelli F.

AU - Komarova, Ekaterina S.

AU - Kasatsky, Pavel

AU - Kartsev, Victor G.

AU - Bogdanov, Alexey A.

AU - Dontsova, Olga A.

AU - Konevega, Andrey L.

AU - Sergiev, Petr V.

AU - Polikanov, Yury S.

PY - 2017

DA - 2017/05/13

PB - Oxford University Press (OUP)

SP - 7507-7514

IS - 12

VL - 45

SN - 0305-1048

SN - 1362-4962

ER -

BibTex |


doi = {10.1093/nar/gkx413},

url = {},

year = 2017,

month = {may},

publisher = {Oxford University Press ({OUP})},

volume = {45},

number = {12},

pages = {7507--7514},

author = {Ilya A. Osterman and Nelli F. Khabibullina and Ekaterina S. Komarova and Pavel Kasatsky and Victor G. Kartsev and Alexey A. Bogdanov and Olga A. Dontsova and Andrey L. Konevega and Petr V. Sergiev and Yury S. Polikanov},

title = {Madumycin {II} inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state}


Osterman, Ilya A. et al. “Madumycin II Inhibits Peptide Bond Formation by Forcing the Peptidyl Transferase Center into an Inactive State.” Nucleic Acids Research 45.12 (2017): 7507–7514. Crossref. Web.