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

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

  • Eleonora S Paulsen, University of Copenhagen, Denmark
  • Jesper Villadsen, University of Copenhagen, Denmark
  • Eleonora Tenori, University of Copenhagen, Denmark
  • Huizhen Liu, University of Copenhagen, Denmark
  • Ditte Fast Bonde, Denmark
  • Mette Alstrup Lie
  • ,
  • Maike Bublitz, Denmark
  • Claus Olesen
  • Henriette Elisabeth Autzen, Denmark
  • Ingrid Dach, Denmark
  • Pankaj Sehgal, Denmark
  • Poul Nissen
  • Jesper Vuust Møller, Denmark
  • Birgit Schiøtt
  • SB Christensen
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 languageEnglish
JournalJournal of Medicinal Chemistry
Pages (from-to)3609-3619
Number of pages9
Publication statusPublished - Apr 2013

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