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Structural basis for vitamin D receptor agonism by novel non‐secosteroidal ligands
Author(s) -
Asano Lisa,
Ito Ichiaki,
Kuwabara Naoyuki,
Waku Tsuyoshi,
Yanagisawa Junn,
Miyachi Hiroyuki,
Shimizu Toshiyuki
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.02.028
Subject(s) - calcitriol receptor , chemistry , agonism , potency , ligand (biochemistry) , agonist , hydrogen bond , stereochemistry , partial agonist , functional selectivity , receptor , helix (gastropod) , biochemistry , molecule , biology , in vitro , politics , organic chemistry , snail , political science , law , ecology
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.