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

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.

journal_name

Sci Adv

journal_title

Science advances

authors

Terekhov SS,Mokrushina YA,Nazarov AS,Zlobin A,Zalevsky A,Bourenkov G,Golovin A,Belogurov A Jr,Osterman IA,Kulikova AA,Mitkevich VA,Lou HJ,Turk BE,Wilmanns M,Smirnov IV,Altman S,Gabibov AG

doi

10.1126/sciadv.aaz9861

subject

Has Abstract

pub_date

2020-06-24 00:00:00

pages

eaaz9861

issue

26

issn

2375-2548

pii

aaz9861

journal_volume

6

pub_type

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