Aarhus University Seal / Aarhus Universitets segl

The C-terminal cavity of the Na,K-ATPase analyzed by docking and electrophysiology

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

The C-terminal cavity of the Na,K-ATPase analyzed by docking and electrophysiology. / Paulsen, Peter Aasted; Jurkowski, Wiktor; Apostolov, Rossen; Lindahl, Erik; Nissen, Poul; Poulsen, Hanne.

In: Molecular Membrane Biology, Vol. 30, No. 2, 03.2013, p. 195-205.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Paulsen, PA, Jurkowski, W, Apostolov, R, Lindahl, E, Nissen, P & Poulsen, H 2013, 'The C-terminal cavity of the Na,K-ATPase analyzed by docking and electrophysiology', Molecular Membrane Biology, vol. 30, no. 2, pp. 195-205. https://doi.org/10.3109/09687688.2012.713520

APA

Paulsen, P. A., Jurkowski, W., Apostolov, R., Lindahl, E., Nissen, P., & Poulsen, H. (2013). The C-terminal cavity of the Na,K-ATPase analyzed by docking and electrophysiology. Molecular Membrane Biology, 30(2), 195-205. https://doi.org/10.3109/09687688.2012.713520

CBE

Paulsen PA, Jurkowski W, Apostolov R, Lindahl E, Nissen P, Poulsen H. 2013. The C-terminal cavity of the Na,K-ATPase analyzed by docking and electrophysiology. Molecular Membrane Biology. 30(2):195-205. https://doi.org/10.3109/09687688.2012.713520

MLA

Vancouver

Paulsen PA, Jurkowski W, Apostolov R, Lindahl E, Nissen P, Poulsen H. The C-terminal cavity of the Na,K-ATPase analyzed by docking and electrophysiology. Molecular Membrane Biology. 2013 Mar;30(2):195-205. https://doi.org/10.3109/09687688.2012.713520

Author

Paulsen, Peter Aasted ; Jurkowski, Wiktor ; Apostolov, Rossen ; Lindahl, Erik ; Nissen, Poul ; Poulsen, Hanne. / The C-terminal cavity of the Na,K-ATPase analyzed by docking and electrophysiology. In: Molecular Membrane Biology. 2013 ; Vol. 30, No. 2. pp. 195-205.

Bibtex

@article{b1aa393cadee4734a9c8b81647bad049,
title = "The C-terminal cavity of the Na,K-ATPase analyzed by docking and electrophysiology",
abstract = "Abstract The Na,K-ATPase is essential to all animals, since it maintains the electrochemical gradients that energize the plasma membrane. Naturally occurring inhibitors of the pump from plants have been used pharmaceutically in cardiac treatment for centuries. The inhibitors block the pump by binding on its extracellular side and thereby locking it. To explore the possibilities for designing an alternative way of targeting the pump function, we have examined the structural requirements for binding to a pocket that accommodates the two C-terminal residues, YY, in the crystal structures of the pump. To cover the sample space of two residues, we first performed docking studies with the 400 possible dipeptides. For validation of the in silico predictions, pumps with 13 dipeptide sequences replacing the C-terminal YY were expressed in Xenopus laevis oocytes and examined with electrophysiology. Our data show a significant correlation between the docking scores from two different methods and the experimentally determined sodium affinities, which strengthens the previous hypothesis that sodium binding is coupled to docking of the C-terminus. From the dipeptides that dock the best and better than wild-type YY, it may therefore be possible to develop specific drugs targeting a previously unexplored binding pocket in the sodium pump.",
author = "Paulsen, {Peter Aasted} and Wiktor Jurkowski and Rossen Apostolov and Erik Lindahl and Poul Nissen and Hanne Poulsen",
year = "2013",
month = mar,
doi = "10.3109/09687688.2012.713520",
language = "English",
volume = "30",
pages = "195--205",
journal = "Molecular Membrane Biology",
issn = "0968-7688",
publisher = "Taylor & Francis ",
number = "2",

}

RIS

TY - JOUR

T1 - The C-terminal cavity of the Na,K-ATPase analyzed by docking and electrophysiology

AU - Paulsen, Peter Aasted

AU - Jurkowski, Wiktor

AU - Apostolov, Rossen

AU - Lindahl, Erik

AU - Nissen, Poul

AU - Poulsen, Hanne

PY - 2013/3

Y1 - 2013/3

N2 - Abstract The Na,K-ATPase is essential to all animals, since it maintains the electrochemical gradients that energize the plasma membrane. Naturally occurring inhibitors of the pump from plants have been used pharmaceutically in cardiac treatment for centuries. The inhibitors block the pump by binding on its extracellular side and thereby locking it. To explore the possibilities for designing an alternative way of targeting the pump function, we have examined the structural requirements for binding to a pocket that accommodates the two C-terminal residues, YY, in the crystal structures of the pump. To cover the sample space of two residues, we first performed docking studies with the 400 possible dipeptides. For validation of the in silico predictions, pumps with 13 dipeptide sequences replacing the C-terminal YY were expressed in Xenopus laevis oocytes and examined with electrophysiology. Our data show a significant correlation between the docking scores from two different methods and the experimentally determined sodium affinities, which strengthens the previous hypothesis that sodium binding is coupled to docking of the C-terminus. From the dipeptides that dock the best and better than wild-type YY, it may therefore be possible to develop specific drugs targeting a previously unexplored binding pocket in the sodium pump.

AB - Abstract The Na,K-ATPase is essential to all animals, since it maintains the electrochemical gradients that energize the plasma membrane. Naturally occurring inhibitors of the pump from plants have been used pharmaceutically in cardiac treatment for centuries. The inhibitors block the pump by binding on its extracellular side and thereby locking it. To explore the possibilities for designing an alternative way of targeting the pump function, we have examined the structural requirements for binding to a pocket that accommodates the two C-terminal residues, YY, in the crystal structures of the pump. To cover the sample space of two residues, we first performed docking studies with the 400 possible dipeptides. For validation of the in silico predictions, pumps with 13 dipeptide sequences replacing the C-terminal YY were expressed in Xenopus laevis oocytes and examined with electrophysiology. Our data show a significant correlation between the docking scores from two different methods and the experimentally determined sodium affinities, which strengthens the previous hypothesis that sodium binding is coupled to docking of the C-terminus. From the dipeptides that dock the best and better than wild-type YY, it may therefore be possible to develop specific drugs targeting a previously unexplored binding pocket in the sodium pump.

U2 - 10.3109/09687688.2012.713520

DO - 10.3109/09687688.2012.713520

M3 - Journal article

C2 - 22913437

VL - 30

SP - 195

EP - 205

JO - Molecular Membrane Biology

JF - Molecular Membrane Biology

SN - 0968-7688

IS - 2

ER -