Potent synthetic and endogenous ligands for the adopted orphan nuclear receptor Nurr1.
Exp Mol Med
; 53(1): 19-29, 2021 01.
Article
de En
| MEDLINE
| ID: mdl-33479411
ABSTRACT
Until recently, Nurr1 (NR4A2) was known as an orphan nuclear receptor without a canonical ligand-binding domain, featuring instead a narrow and tight cavity for small molecular ligands to bind. In-depth characterization of its ligand-binding pocket revealed that it is highly dynamic, with its structural conformation changing more than twice on the microsecond-to-millisecond timescale. This observation suggests the possibility that certain ligands are able to squeeze into this narrow space, inducing a conformational change to create an accessible cavity. The cocrystallographic structure of Nurr1 bound to endogenous ligands such as prostaglandin E1/A1 and 5,6-dihydroxyindole contributed to clarifying the crucial roles of Nurr1 and opening new avenues for therapeutic interventions for neurodegenerative and/or inflammatory diseases related to Nurr1. This review introduces novel endogenous and synthetic Nurr1 agonists and discusses their potential effects in Nurr1-related diseases.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Membre-2 du groupe A de la sous-famille-4 de récepteurs nucléaires
Limites:
Animals
/
Humans
Langue:
En
Journal:
Exp Mol Med
Sujet du journal:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Année:
2021
Type de document:
Article