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DNA replication machinery and topoisomerases – good targets for new antibiotics developmentстатья Тезисы
Информация о цитировании статьи получена из
Web of Science
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 8 января 2021 г.
- Авторы: OstermanI I., Shiriaev D., Sofronova A., Khven I., Lukianov D., Komarova E., Zakalyukina Y., Maviza T., Birykov M., Ivanenkov Y., Sergiev P., Dontsova O.
- Журнал: FEBS open bio
- Том: 9
- Год издания: 2019
- Издательство: John Wiley & Sons Inc.
- Местоположение издательства: United States
- Первая страница: 149
- Последняя страница: 149
- Номер статьи: P-08-007
- DOI: 10.1002/2211-5463.12675
- Аннотация: Due to spread of the resistance to classic antibiotics, development of the new antibacterial agents becomes one of the principal goal of the modern biotechnology.Fluoroquinolones (FQ), one of the first discovered inhibitors of the bacterial topoisomerases (Topo IV and gyrase) are effective against wide range of gramnegativeand grampositivebacteria. Meanwhile resistance to these drugs due to mutations in the targets significantly increases during last years.Recently, we developed highthroughputfluorescent approach for discovering antibiotics, affecting DNA replication machinery (1). Nybomycin, old, but not wellstudiedantibiotic, was one of the compounds, which induced our reporter in E.coli cells. We demonstrated, that Nybomycin inhibits activity of both wildtypeand FQresistantgyrase (gyrA: Ser83Leu), but another mutation (gyrA: Tyr87Asp) gives gyrase resistance to FQ and Nybomycin. Molecular docking experiments predictsbinding place on gyrase for Nybomycin close to FQ, but position of the drug is different. The mechanism of nybomycin action is also different from FQ, latter inhibitDNA ligation after double break, but Nybomycin prevents double break formation.Like FQ, Nybomycin acts on bacterial DNA topoisomerase IV, but unlike latter it also inhibits eukaryotic topoisomerase 2α. In addition to type IItopoisomerases, which cut both strands of the DNA, Nybomycin acts on type I topoisomerases from bacteria and eukaryotes. Our work demonstrates, that naturalantibacterial agent Nybomycin inhibits activity of different DNA topoisomerases, so it is good candidate for antibacterial agents design, because simultaneous resistantmutations in different targets is rare event. Inhibition of eukaryotic topoisomerase could be used for development of the anticancer agent.
- Добавил в систему: Бирюков Михаил Владимирович