Электронный каталог

Статья

Kolosova, O.
Mechanism of Read-Through Enhancement by Aminoglycosides and Mefloquine / O.Kolosova, A.Rogachev, [a.o.]. – Text : electronic // PNAS : The Proceedings of the National Academy of Sciences of the United States of America. – 2025. – Vol. 122, No. 17. – P. e2420261122. – URL: https://doi.org/10.1073/pnas.2420261122. – Bibliogr.: 85.

Nonsense mutations are associated with numerous and diverse pathologies, yet effective treatment strategies remain elusive. A promising approach to combat these conditions involves the use of aminoglycosides, particularly in combination with stop-codon read-through enhancers, for developing drugs that can rescue the production of full-length proteins. Using X-ray crystallography and single-particle cryo-EM, we obtained structures of the eukaryotic ribosome in complexes with several aminoglycosides (geneticin G418, paromomycin, and hygromycin B) and the antimalarial drug mefloquine (MFQ), which has also been identified as a read-through enhancer. Our study reveals a binding site of MFQ, which holds significant promise for the development of therapies targeting premature termination codon-related genetic and oncological diseases. The results underscore the crucial role of the bridge B7b/c in mediating the effects of MFQ on subunit rotation dynamics. Through a comprehensive analysis of the interactions between the drugs and the eukaryotic ribosome, we propose a unifying hypothesis for read-through enhancement by small molecules, highlighting the role of decoding center rearrangements and intersubunit rotation dynamics.



ОИЯИ = ОИЯИ (JINR)2025
Спец.(статьи,препринты) = 28.0 - Биология$
Спец.(статьи,препринты) = С 332.8 - Синхротронное излучение. Лазеры на свободных электронах. Получение и использование рентгеновских лучей
Спец.(статьи,препринты) = С 350 - Приложения методов ядерной физики в смежных областях
Бюллетени = 39/025