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.
Original language | English (US) |
---|---|
Article number | eaaz9861 |
Journal | Science Advances |
Volume | 6 |
Issue number | 26 |
DOIs | |
State | Published - Jun 2020 |
ASJC Scopus subject areas
- General
Fingerprint
Dive into the research topics of 'A kinase bioscavenger provides antibiotic resistance by extremely tight substrate binding'. Together they form a unique fingerprint.Datasets
-
AMICOUMACIN KINASE AMIN
Terekhov, S. S. (Contributor), Mokrushina, Y. A. (Contributor), Nazarov, A. S. (Contributor), Zlobin, A. (Contributor), Zalevsky, A. (Contributor), Bourenkov, G. (Contributor), Golovin, A. (Contributor), Belogurov, A. (Contributor), Osterman, I. A. (Contributor), Kulikova, A. A. (Contributor), Mitkevich, V. A. (Contributor), Lou, H. J. (Contributor), Turk, B. E. (Contributor), Wilmanns, M. (Contributor), Smirnov, I. V. (Contributor), Altman, S. (Contributor) & Gabibov, A. G. (Contributor), Protein Data Bank (PDB), Jul 22 2020
DOI: 10.2210/pdb6SUI/pdb, https://www.wwpdb.org/pdb?id=pdb_00006sui
Dataset
-
Amicoumacin kinase AmiN in complex with ATP
Terekhov, S. S. (Contributor), Mokrushina, Y. A. (Contributor), Nazarov, A. S. (Contributor), Zlobin, A. (Contributor), Zalevsky, A. (Contributor), Bourenkov, G. (Contributor), Golovin, A. (Contributor), Belogurov, A. (Contributor), Osterman, I. A. (Contributor), Kulikova, A. A. (Contributor), Mitkevich, V. A. (Contributor), Lou, H. J. (Contributor), Turk, B. E. (Contributor), Wilmanns, M. (Contributor), Smirnov, I. V. (Contributor), Altman, S. (Contributor) & Gabibov, A. G. (Contributor), Protein Data Bank (PDB), Jul 22 2020
DOI: 10.2210/pdb6SV5/pdb, https://www.wwpdb.org/pdb?id=pdb_00006sv5
Dataset
-
Amicoumacin kinase hAmiN in complex with AMP-PNP, Ca2+ and Ami
Terekhov, S. S. (Contributor), Mokrushina, Y. A. (Contributor), Nazarov, A. S. (Contributor), Zlobin, A. (Contributor), Zalevsky, A. (Contributor), Bourenkov, G. (Contributor), Golovin, A. (Contributor), Belogurov, A. (Contributor), Osterman, I. A. (Contributor), Kulikova, A. A. (Contributor), Mitkevich, V. A. (Contributor), Lou, H. J. (Contributor), Turk, B. E. (Contributor), Wilmanns, M. (Contributor), Smirnov, I. V. (Contributor), Altman, S. (Contributor) & Gabibov, A. G. (Contributor), Protein Data Bank (PDB), Jul 22 2020
DOI: 10.2210/pdb6SUN/pdb, https://www.wwpdb.org/pdb?id=pdb_00006sun
Dataset