Water-mediated interactions influence the binding of thapsigargin to sarco/endoplasmic reticulum calcium adenosinetriphosphatase

Eleonora S Paulsen; Jesper Villadsen; Eleonora Tenori; Huizhen Liu; Ditte Fast Bonde; Mette Alstrup Lie; Maike Bublitz; Claus Olesen; Henriette Elisabeth Autzen; Ingrid Dach; Pankaj Sehgal; Poul Nissen; Jesper Vuust Møller; Birgit Schiøtt; SB Christensen

doi:10.1021/jm4001083

Water-mediated interactions influence the binding of thapsigargin to sarco/endoplasmic reticulum calcium adenosinetriphosphatase

Eleonora S Paulsen, Jesper Villadsen, Eleonora Tenori, Huizhen Liu, Ditte Fast Bonde, Mette Alstrup Lie, Maike Bublitz, Claus Olesen, Henriette Elisabeth Autzen, Ingrid Dach, Pankaj Sehgal, Poul Nissen, Jesper Vuust Møller, Birgit Schiøtt, SB Christensen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

24 Citations (Scopus)

Abstract

A crystal structure suggests four water molecules are present in the binding cavity of thapsigargin in sarco/endoplasmic reticulum calcium ATPase (SERCA). Computational chemistry indicates that three of these water molecules mediate an extensive hydrogen-bonding network between thapsigargin and the backbone of SERCA. The orientation of the thapsigargin molecule in SERCA is crucially dependent on these interactions. The hypothesis has been verified by measuring the affinity of newly synthesized model compounds, which are prevented from participating in such water-mediated interactions as hydrogen-bond donors

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	56
Issue	9
Pages (from-to)	3609-3619
Number of pages	9
ISSN	0022-2623
DOIs	https://doi.org/10.1021/jm4001083
Publication status	Published - Apr 2013

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Paulsen, E. S., Villadsen, J., Tenori, E., Liu, H., Bonde, D. F., Lie, M. A., Bublitz, M., Olesen, C., Autzen, H. E., Dach, I., Sehgal, P., Nissen, P., Møller, J. V., Schiøtt, B., & Christensen, SB. (2013). Water-mediated interactions influence the binding of thapsigargin to sarco/endoplasmic reticulum calcium adenosinetriphosphatase. Journal of Medicinal Chemistry, 56(9), 3609-3619. https://doi.org/10.1021/jm4001083

@article{6a104b41741f4e6ab9973464529a6485,

title = "Water-mediated interactions influence the binding of thapsigargin to sarco/endoplasmic reticulum calcium adenosinetriphosphatase",

abstract = "A crystal structure suggests four water molecules are present in the binding cavity of thapsigargin in sarco/endoplasmic reticulum calcium ATPase (SERCA). Computational chemistry indicates that three of these water molecules mediate an extensive hydrogen-bonding network between thapsigargin and the backbone of SERCA. The orientation of the thapsigargin molecule in SERCA is crucially dependent on these interactions. The hypothesis has been verified by measuring the affinity of newly synthesized model compounds, which are prevented from participating in such water-mediated interactions as hydrogen-bond donors",

author = "Paulsen, {Eleonora S} and Jesper Villadsen and Eleonora Tenori and Huizhen Liu and Bonde, {Ditte Fast} and Lie, {Mette Alstrup} and Maike Bublitz and Claus Olesen and Autzen, {Henriette Elisabeth} and Ingrid Dach and Pankaj Sehgal and Poul Nissen and M{\o}ller, {Jesper Vuust} and Birgit Schi{\o}tt and SB Christensen",

year = "2013",

month = apr,

doi = "10.1021/jm4001083",

language = "English",

volume = "56",

pages = "3609--3619",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "9",

}

Paulsen, ES, Villadsen, J, Tenori, E, Liu, H, Bonde, DF, Lie, MA, Bublitz, M, Olesen, C, Autzen, HE, Dach, I, Sehgal, P, Nissen, P, Møller, JV, Schiøtt, B & Christensen, SB 2013, 'Water-mediated interactions influence the binding of thapsigargin to sarco/endoplasmic reticulum calcium adenosinetriphosphatase', Journal of Medicinal Chemistry, vol. 56, no. 9, pp. 3609-3619. https://doi.org/10.1021/jm4001083

Water-mediated interactions influence the binding of thapsigargin to sarco/endoplasmic reticulum calcium adenosinetriphosphatase. / Paulsen, Eleonora S; Villadsen, Jesper; Tenori, Eleonora et al.
In: Journal of Medicinal Chemistry, Vol. 56, No. 9, 04.2013, p. 3609-3619.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Water-mediated interactions influence the binding of thapsigargin to sarco/endoplasmic reticulum calcium adenosinetriphosphatase

AU - Paulsen, Eleonora S

AU - Villadsen, Jesper

AU - Tenori, Eleonora

AU - Liu, Huizhen

AU - Bonde, Ditte Fast

AU - Lie, Mette Alstrup

AU - Bublitz, Maike

AU - Olesen, Claus

AU - Autzen, Henriette Elisabeth

AU - Dach, Ingrid

AU - Sehgal, Pankaj

AU - Nissen, Poul

AU - Møller, Jesper Vuust

AU - Schiøtt, Birgit

AU - Christensen, SB

PY - 2013/4

Y1 - 2013/4

N2 - A crystal structure suggests four water molecules are present in the binding cavity of thapsigargin in sarco/endoplasmic reticulum calcium ATPase (SERCA). Computational chemistry indicates that three of these water molecules mediate an extensive hydrogen-bonding network between thapsigargin and the backbone of SERCA. The orientation of the thapsigargin molecule in SERCA is crucially dependent on these interactions. The hypothesis has been verified by measuring the affinity of newly synthesized model compounds, which are prevented from participating in such water-mediated interactions as hydrogen-bond donors

AB - A crystal structure suggests four water molecules are present in the binding cavity of thapsigargin in sarco/endoplasmic reticulum calcium ATPase (SERCA). Computational chemistry indicates that three of these water molecules mediate an extensive hydrogen-bonding network between thapsigargin and the backbone of SERCA. The orientation of the thapsigargin molecule in SERCA is crucially dependent on these interactions. The hypothesis has been verified by measuring the affinity of newly synthesized model compounds, which are prevented from participating in such water-mediated interactions as hydrogen-bond donors

U2 - 10.1021/jm4001083

DO - 10.1021/jm4001083

M3 - Journal article

C2 - 23574308

SN - 0022-2623

VL - 56

SP - 3609

EP - 3619

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 9

ER -

Water-mediated interactions influence the binding of thapsigargin to sarco/endoplasmic reticulum calcium adenosinetriphosphatase

Abstract

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