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  • A kinase bioscavenger provides antibiotic resistance by extremely tight substrate binding.

A kinase bioscavenger provides antibiotic resistance by extremely tight substrate binding.

Science advances (2020-07-09)
Stanislav S Terekhov, Yuliana A Mokrushina, Anton S Nazarov, Alexander Zlobin, Arthur Zalevsky, Gleb Bourenkov, Andrey Golovin, Alexey Belogurov, Ilya A Osterman, Alexandra A Kulikova, Vladimir A Mitkevich, Hua Jane Lou, Benjamin E Turk, Matthias Wilmanns, Ivan V Smirnov, Sidney Altman, Alexander G Gabibov
ABSTRACT

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.

MATERIALS
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Product Description

Sigma-Aldrich
D-Glucosamine 6-phosphate, ≥98% (TLC)