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Berberine analog of chloramphenicol exhibits a distinct mode of action and unveils ribosome plasticityстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Batool Zahra, Pavlova Julia A., Paranjpe Madhura N., Tereshchenkov Andrey G., Lukianov Dmitrii A., Osterman Ilya A., Bogdanov Alexey A., Sumbatyan Natalia V., Polikanov Yury S.
- Журнал: Structure
- Том: 32
- Год издания: 2024
- Издательство: Cell Press
- Местоположение издательства: United States
- Первая страница: 1
- Последняя страница: 14
- DOI: 10.1016/j.str.2024.06.013
- Аннотация: Chloramphenicol (CHL) is an antibiotic targeting the peptidyl transferase center in bacterial ribosomes. We synthesized a new analog, CAM-BER, by substituting the dichloroacetyl moiety of CHL with a positively charged aromatic berberine group. CAM-BER suppresses bacterial cell growth, inhibits protein synthesis in vitro, and binds tightly to the 70S ribosome. Crystal structure analysis reveals that the bulky berberine group folds into the P site of the peptidyl transferase center (PTC), where it competes with the formyl-methionine residue of the initiator tRNA. Our toe-printing data confirm that CAM-BER acts as a translation initiation inhibitor in stark contrast to CHL, a translation elongation inhibitor. Moreover, CAM-BER induces a distinct rearrangement of conformationally restrained nucleotide A2059, suggesting that the 23S rRNA plasticity is significantly higher than previously thought. CAM-BER shows potential in avoiding CHL resistance and presents opportunities for developing novel berberine derivatives of CHL through medicinal chemistry exploration.
- Добавил в систему: Голубева Юлия Анатольевна