A kinase bioscavenger provides antibiotic resistance by extremely tight substrate binding.
Microbial communities are self-controlled by repertoires of lethal agents, the antibiotics. In their turn, these antibiotics are regulated by bioscavengers that are selected in the course of evolution. Kinase-mediated phosphorylation represents one of the general strategies for the emergence of antibiotic resistance. A new subfamily of AmiN-like kinases, isolated from the Siberian bear microbiome, inactivates antibiotic amicoumacin by phosphorylation. The nanomolar substrate affinity defines AmiN as a phosphotransferase with a unique catalytic efficiency proximal to the diffusion limit. Crystallographic analysis and multiscale simulations revealed a catalytically perfect mechanism providing phosphorylation exclusively in the case of a closed active site that counteracts substrate promiscuity. AmiN kinase is a member of the previously unknown subfamily representing the first evidence of a specialized phosphotransferase bioscavenger.
Список научных проектов, где отмечена публикация
- Изучение молекулярных механизмов резистентности, обусловленных активностью ферментов модификации изокумариновых антибиотиков (6 Января 2019 года 31 Декабря 2020 года). . Грант, РФФИ.
- Создание искусственных библиотек кластеров генов биосинтеза лантибиотиков (7 Августа 2018 года 7 Декабря 2021 года). . Грант, РФФИ.