Evolution of cation binding in the active sites of P-loop nucleoside triphosphatases in relation to the basic catalytic mechanism
- University of Osnabrück, Germany
- Lomonosov Moscow State University, Russian Federation
- National Institutes of Health, United States
Abstract
The ubiquitous P-loop fold nucleoside triphosphatases (NTPases) are typically activated by an arginine or lysine 'finger'. Some of the apparently ancestral NTPases are, instead, activated by potassium ions. To clarify the activation mechanism, we combined comparative structure analysis with molecular dynamics (MD) simulations of Mg-ATP and Mg-GTP complexes in water and in the presence of potassium, sodium, or ammonium ions. In all analyzed structures of diverse P-loop NTPases, the conserved P-loop motif keeps the triphosphate chain of bound NTPs (or their analogs) in an extended, catalytically prone conformation, similar to that imposed on NTPs in water by potassium or ammonium ions. MD simulations of potassium-dependent GTPase MnmE showed that linking of alpha- and gamma phosphates by the activating potassium ion led to the rotation of the gamma-phosphate group yielding an almost eclipsed, catalytically productive conformation of the triphosphate chain, which could represent the basic mechanism of hydrolysis by P-loop NTPases.
Data availability
As obtained from MD simulations, we provide the structures of Mg-ATP complexes with bound K+, Na+ or NH4+ ions, as well as the structures of the G-domains of MnmE GTPases with and w/o activating potassium ions as source data files. Simulation data sets have been uploaded to Zenodo (https://zenodo.org/record/1888492#.XAasVhP7RTY).
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Molecular Dynamics simulation data for the articleZenodo, 10.5281/zenodo.1888492.
Article and author information
Author details
Michael Y Galperin
Armen Y Mulkidjanian
Funding
Deutsche Forschungsgemeinschaft (N/A)
- Armen Y Mulkidjanian
Bundesministerium für Bildung und Forschung (Laseromix)
- Armen Y Mulkidjanian
Deutscher Akademischer Austauschdienst (Ostpartnerschaftenprogramm)
- Daria N Shalaeva
Russian Science Foundation (14-50-00029)
- Daria N Shalaeva
- Dmitry A Cherepanov
U.S. National Library of Medicine (Intramural Research Program)
- Michael Y Galperin
Lomonosov Moscow State University (RFMEFI62117X0011)
- Andrey V Golovin
Osnabrueck University, Germany (EvoCell Program)
- Armen Y Mulkidjanian
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Evolution of cation binding in the active sites of P-loop nucleoside triphosphatases in relation to the basic catalytic mechanism
eLife 7:e37373.
https://doi.org/10.7554/eLife.37373
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