Elucidation of the topography of the thapsigargin binding site in the sarco-endoplasmic calcium ATPase

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Dorthe Mondrup Skytte
  • Jesper Vuust Møller
  • Huizhen Liu
  • Helle Østergren Nielsen
  • Louise Elsa Svenningsen
  • Christina Mernøe Jensen
  • Carl Erik Olsen
  • Christensen, Søren Brøgger
Removal of each of the acyl groups of thapsigargin at O-3, O-8 and O-10 significant reduces the affinity of the inhibitors to the SERCA1a pump. Replacement of the acyl groups at O-3 and O-10 with flexible residues could be performed with only a minor decrease of the affinity, whereas introduction of voluminous stiff residues caused dramatic reduction of the affinity. The results can be rationalized on the basis of the interactions of thapsigargin with the SERCA1a pump as revealed from 3D X-ray structural models of thapsigargin bound to the SERCA1a. In conclusion the results confirm and elaborate the previously suggested pharmocophore model of thapsigargin.
TidsskriftBioorganic & Medicinal Chemistry
Udgave nummer15
Sider (fra-til)5634-5646
Antal sider13
StatusUdgivet - 2010

ID: 21858685