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Binding action of amino-acid analogues of chloramphenicol upon the bacterial ribosomeстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 24 апреля 2018 г.
- Авторы: Tereshchenkov A.G., Dobosz-Bartoszek М., Osterman I.A., Marks J., Sergeeva V.A., Kasatsky P., Komarova E.S., Stavrianidi A.A., Rodin I.A., Konevega A.L., Sergiev P.V., Sumbatyan N.V., Mankin A.S., Bogdanov A.A., Polikanov Y.S.
- Журнал: Journal of Molecular Biology
- Том: 430
- Номер: 6
- Год издания: 2018
- Издательство: Academic Press
- Местоположение издательства: United States
- Первая страница: 842
- Последняя страница: 852
- DOI: 10.1016/j.jmb.2018.01.016
- Аннотация: Antibiotic chloramphenicol (CHL) binds with a moderate affinity at the peptidyl transferase center of the bacterial ribosome and inhibits peptide bond formation. As an approach for modifying and potentially improving properties of this inhibitor, we explored ribosome binding and inhibitory activity of a number of amino-acid analogues of CHL. The L-histidyl analogue binds to the ribosome with the affinity exceeding that of CHL by 10 fold. Several of the newly synthesized analogues were able to inhibit protein synthesis and exhibited the mode of action that was distinct from the action of CHL. However, the inhibitory properties of the semi-synthetic CHL-analogues did not correlate with their affinity and in general, the amino-acid analogues of CHL were less active inhibitors of translation in comparison with the original antibiotic. The X-ray crystal structures of the Thermus thermophilus 70S ribosome in complex with three semi-synthetic analogues showed that CHL derivatives bind at the peptidyl transferase center, where the aminoacyl moiety of the tested compounds established idiosyncratic interactions with rRNA. Although still fairly inefficient inhibitors of translation, the synthesized compounds represent promising chemical scaffolds that target the peptidyl transferase center of the ribosome and potentially are suitable for further exploration.
- Добавил в систему: Родин Игорь Александрович