Lytic water dynamics reveal evolutionarily conserved mechanisms of ATP hydrolysis by TIP49 AAA+ ATPases. Afanasyeva, A., Hirtreiter, A., Schreiber, A., Grohmann, D., Pobegalov, G., McKay, A., Tsaneva, I., Petukhov, M., Käs, E., Grigoriev, M., & Werner, F. Structure, 22(4):549-559, 2014. cited By 12
Lytic water dynamics reveal evolutionarily conserved mechanisms of ATP hydrolysis by TIP49 AAA+ ATPases [link]Paper  doi  abstract   bibtex   
Eukaryotic TIP49a (Pontin) and TIP49b (Reptin) AAA+ ATPases play essential roles in key cellular processes. How their weak ATPase activity contributes to their important functions remains largely unknown and difficult to analyze because of the divergent properties of TIP49a and TIP49b proteins and of their homo- and hetero-oligomeric assemblies. To circumvent these complexities, we have analyzed the single ancient TIP49 ortholog found in the archaeon Methanopyrus kandleri (mkTIP49). All-atom homology modeling and molecular dynamics simulations validated by biochemical assays reveal highly conserved organizational principles and identify key residues for ATP hydrolysis. An unanticipated crosstalk between Walker B and Sensor I motifs impacts the dynamics of water molecules and highlights a critical role of trans-acting aspartates in the lytic water activation step that is essential for the associative mechanism of ATP hydrolysis. © 2014 The Authors.
@ARTICLE{Afanasyeva2014549,
author={Afanasyeva, A. and Hirtreiter, A. and Schreiber, A. and Grohmann, D. and Pobegalov, G. and McKay, A.R. and Tsaneva, I. and Petukhov, M. and Käs, E. and Grigoriev, M. and Werner, F.},
title={Lytic water dynamics reveal evolutionarily conserved mechanisms of ATP hydrolysis by TIP49 AAA+ ATPases},
journal={Structure},
year={2014},
volume={22},
number={4},
pages={549-559},
doi={10.1016/j.str.2014.02.002},
note={cited By 12},
url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-84898431978&doi=10.1016%2fj.str.2014.02.002&partnerID=40&md5=d0de41cbac2f5d2f3463f48082ae0b53},
affiliation={Department of Biophysics, Saint Petersburg State Polytechnical University, Saint-Petersburg 195251, Russian Federation; Division of Biosciences, Institute for Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom; Physikalische und Theoretische Chemie - NanoBioSciences, Technische Universität Braunschweig, Braunschweig 38106, Germany; Department of Chemistry, University College London, London WC1H 0AJ, United Kingdom; Division of Molecular and Radiation Biophysics, Petersburg Nuclear Physics Institute, Gatchina 188300, Russian Federation; UMR 5099, CNRS, Toulouse F-31000, France; Laboratoire de Biologie Moléculaire Eucaryote, Université de Toulouse, Toulouse F-31000, France; Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, United Kingdom},
abstract={Eukaryotic TIP49a (Pontin) and TIP49b (Reptin) AAA+ ATPases play essential roles in key cellular processes. How their weak ATPase activity contributes to their important functions remains largely unknown and difficult to analyze because of the divergent properties of TIP49a and TIP49b proteins and of their homo- and hetero-oligomeric assemblies. To circumvent these complexities, we have analyzed the single ancient TIP49 ortholog found in the archaeon Methanopyrus kandleri (mkTIP49). All-atom homology modeling and molecular dynamics simulations validated by biochemical assays reveal highly conserved organizational principles and identify key residues for ATP hydrolysis. An unanticipated crosstalk between Walker B and Sensor I motifs impacts the dynamics of water molecules and highlights a critical role of trans-acting aspartates in the lytic water activation step that is essential for the associative mechanism of ATP hydrolysis. © 2014 The Authors.},
funding_details={Wellcome Trust079351/Z/06/Z},
funding_details={Biotechnology and Biological Sciences Research CouncilBB/E008232/1},
funding_details={Ministry of Education and Science of the Russian Federation11.519.11.2002},
}

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