Evolution of cation binding in the active sites of P-loop nucleoside triphosphatases in relation to the basic catalytic mechanism

  1. Daria N Shalaeva
  2. Dmitry A Cherepanov
  3. Michael Y Galperin
  4. Andrey V Golovin
  5. Armen Y Mulkidjanian  Is a corresponding author
  1. University of Osnabrück, Germany
  2. Lomonosov Moscow State University, Russian Federation
  3. 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).

The following data sets were generated

Article and author information

Author details

  1. Daria N Shalaeva

    School of Physics, University of Osnabrück, Osnabrück, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Dmitry A Cherepanov

    A N Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  3. Michael Y Galperin

    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2265-5572
  4. Andrey V Golovin

    School of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  5. Armen Y Mulkidjanian

    School of Physics, University of Osnabrück, Osnabrück, Germany
    For correspondence
    amulkid@uos.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5844-3064

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.

Reviewing Editor

  1. Nick V Grishin, University of Texas Southwestern Medical Center, United States

Version history

  1. Received: April 9, 2018
  2. Accepted: November 26, 2018
  3. Accepted Manuscript published: December 11, 2018 (version 1)
  4. Version of Record published: December 28, 2018 (version 2)

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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  1. Daria N Shalaeva
  2. Dmitry A Cherepanov
  3. Michael Y Galperin
  4. Andrey V Golovin
  5. Armen Y Mulkidjanian
(2018)
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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https://doi.org/10.7554/eLife.37373

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