Investigation of selective inhibition of digoxin derivative on retinoic acid-related orphan nuclear receptorγt transcription activity using molecular docking
10.3969/j.issn.1673-4254.2014.04.16
- VernacularTitle:分子对接分析地高辛衍生物选择性拮抗RORγt活性
- Author:
Caimei ZHONG
1
;
Yixuan CAI
;
Meirong WANG
;
Xiufen ZHENG
;
Xianwen QIU
;
Ledong SUN
;
Fan ZHANG
;
Tangde ZHANG
Author Information
1. 南方医科大学珠江医院皮肤病与性病科
- Keywords:
RORγt;
molecular docking;
digoxin;
immune diease
- From:
Journal of Southern Medical University
2014;(4):511-518
- CountryChina
- Language:Chinese
-
Abstract:
Objetive Psoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated with the dysfunction of Th17 cells. Retinoic acid-related orphan nuclear receptorγt (RORγt) plays a critical role in the differentiation and maturation of Th17 cells and in cell-derived immunologic derangement. We conducted this study to investigate potential mechanism by which the derivative of digoxin selectively antagonizes RORγt transcriptional activity. Method Using molecular docking in combination with molecular electrostatic potential (MEP), we detected the interaction between the derivative of digoxin (Dhd) and ROR transcription factor (RORα,RORβ and RORγt), and the results were further confirmed by bioluminescent assay. Result Molecular docking demonstrated that Dhd could exclusively inhibit the conformation of RORγt;bioluminescent assay further indicated that RORγt was selectively antagonized by Dhd in a dose- and time-dependent manner. Conclusion Dhd can selectively suppress RORγt transcriptional activity.
