Structural basis for vitamin D receptor agonism by novel non-secosteroidal ligands

Lisa Asano, Ichiaki Ito, Naoyuki Kuwabara, Tsuyoshi Waku, Junn Yanagisawa, Hiroyuki Miyachi, Toshiyuki Shimizu

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Non-secosteroidal ligands for vitamin D receptor (VDR) have been developed for the agonist with non-calcemic profiles. Here, we provide the structural mechanism of VDR agonism by novel non-secosteroidal ligands. All ligands had the similar efficacy, while two had the higher potency. Crystallographic analyses revealed that all ligands interacted with helix H10 and the loop between helices H6 and H7 in a similar manner, but also that the two ligands with higher potency had different interaction modes. This study suggests that distinct ligand potency depend upon differences in the formation and rearrangement of hydrogen-bond networks induced by each ligand.

Original languageEnglish (US)
Pages (from-to)957-963
Number of pages7
JournalFEBS Letters
Volume587
Issue number7
DOIs
StatePublished - Apr 2 2013

Keywords

  • Agonism
  • Crystal structure
  • Non-secosteroidal ligand
  • Vitamin D receptor

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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