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


Journal

Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440

Informations de publication

Date de publication:
06 2020
Historique:
received: 25 10 2019
accepted: 16 04 2020
entrez: 9 7 2020
pubmed: 9 7 2020
medline: 9 7 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 32637600
doi: 10.1126/sciadv.aaz9861
pii: aaz9861
pmc: PMC7314540
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

eaaz9861

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM104047
Pays : United States

Informations de copyright

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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Auteurs

Stanislav S Terekhov (SS)

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
Department of Chemistry, Lomonosov Moscow State University, Moscow, Russia.

Yuliana A Mokrushina (YA)

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
Department of Chemistry, Lomonosov Moscow State University, Moscow, Russia.

Anton S Nazarov (AS)

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.

Alexander Zlobin (A)

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.

Arthur Zalevsky (A)

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.
Sechenov First Moscow State Medical University, Institute of Molecular Medicine, Moscow, Russia.

Gleb Bourenkov (G)

European Molecular Biology Laboratory, Hamburg, Germany.

Andrey Golovin (A)

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.
Sechenov First Moscow State Medical University, Institute of Molecular Medicine, Moscow, Russia.

Alexey Belogurov (A)

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.

Ilya A Osterman (IA)

Department of Chemistry, Lomonosov Moscow State University, Moscow, Russia.
Skolkovo Institute of Science and Technology, Skolkovo, Russia.

Alexandra A Kulikova (AA)

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.

Vladimir A Mitkevich (VA)

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.

Hua Jane Lou (HJ)

Department of Pharmacology, Yale School of Medicine, New Haven, CT, USA.

Benjamin E Turk (BE)

Department of Pharmacology, Yale School of Medicine, New Haven, CT, USA.

Matthias Wilmanns (M)

European Molecular Biology Laboratory, Hamburg, Germany.

Ivan V Smirnov (IV)

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
Department of Chemistry, Lomonosov Moscow State University, Moscow, Russia.

Sidney Altman (S)

Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
Arizona State University, Tempe, AZ, USA.

Alexander G Gabibov (AG)

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
Department of Chemistry, Lomonosov Moscow State University, Moscow, Russia.
Department of Life Sciences, Higher School of Economics, Moscow, Russia.

Classifications MeSH