Structural basis for vitamin D receptor agonism by novel non-secosteroidal ligands
Structural basis for vitamin D receptor agonism by novel non-secosteroidal ligands
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DOI：
10.1016/j.febslet.2013.02.028
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发表时间：
2013-04-02
期刊：
影响因子：
3.5
通讯作者：
Shimizu, Toshiyuki
中科院分区：
文献类型：
--
作者：
Asano, Lisa;Ito, Ichiaki;Shimizu, Toshiyuki
维生素D受体（VDR）的非开环甾体配体已被开发用于具有非钙调素特征的激动剂。在这里，我们提供了新的非开环甾体配体的VDR激动的结构机制。所有配体具有相似的效力，而两种配体具有更高的效力。晶体学分析表明，所有的配体与螺旋H10和螺旋H6和H7之间的环以类似的方式相互作用，但也具有较高效力的两个配体具有不同的相互作用模式。这项研究表明，不同的配体效力取决于每个配体诱导的氢键网络的形成和重排的差异。(C)2013年欧洲生物化学学会联合会。由Elsevier B出版。V.保留所有权利。
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. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.