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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Eleonora Sandholdt Paulsen
  • Jesper Villadsen
  • Eleonora Tenori
  • Huizhen Liu
  • Ditte Fast Bonde
  • Mette Alstrup Lie
  • Maike Bublitz
  • Claus Linding Olesen
  • Henriette Elizabeth Autzen
  • Ingrid Dach
  • Pankaj Sehgal
  • Poul Nissen
  • Jesper Møller
  • Birgit Schiøtt
  • Christensen, Søren Brøgger
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.
OriginalsprogEngelsk
TidsskriftJournal of Medicinal Chemistry
Vol/bind56
Udgave nummer9
Sider (fra-til)3609-19
Antal sider11
DOI
StatusUdgivet - 9 maj 2013

ID: 45874326