A kinase bioscavenger provides antibiotic resistance by extremely tight substrate binding
Kinase-mediated phosphorylation represents one of the general strategies for the emergence of antibiotic resistance. Scientists from the Laboratory of biocatalysis reported a unique bioscavenging kinase AmiN, member of 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. The work is published in Science Advances.
june 26, 2020