RORγ Structural Plasticity and Druggability.
Int J Mol Sci
; 21(15)2020 Jul 27.
Article
en En
| MEDLINE
| ID: mdl-32727079
ABSTRACT
Retinoic acid receptor-related orphan receptor γ (RORγ) is a transcription factor regulating the expression of the pro-inflammatory cytokine IL-17 in human T helper 17 (Th17) cells. Activating RORγ can induce multiple IL-17-mediated autoimmune diseases but may also be useful for anticancer therapy. Its deep immunological functions make RORɣ an attractive drug target. Over 100 crystal structures have been published describing atomic interactions between RORɣ and agonists and inverse agonists. In this review, we focus on the role of dynamic properties and plasticity of the RORɣ orthosteric and allosteric binding sites by examining structural information from crystal structures and simulated models. We discuss the possible influences of allosteric ligands on the orthosteric binding site. We find that high structural plasticity favors the druggability of RORɣ, especially for allosteric ligands.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Sistemas de Liberación de Medicamentos
/
Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos