Crystal structure of hereditary vitamin D-resistant rickets--associated mutant H305Q of vitamin D nuclear receptor bound to its natural ligand.
J Steroid Biochem Mol Biol
; 121(1-2): 84-7, 2010 Jul.
Article
en En
| MEDLINE
| ID: mdl-20403435
ABSTRACT
In the nuclear receptor of vitamin D (VDR) histidine 305 participates to the anchoring of the ligand. The VDR H305Q mutation was identified in a patient who exhibited the hereditary vitamin D-resistant rickets (HVDRR). We report the crystal structure of human VDR H305Q-ligand binding domain bound to 1alpha,25(OH)2D3 solved at 1.8A resolution. The protein adopts the active conformation of the wild-type liganded VDR. A local conformational flexibility at the mutation site weakens the hydrogen bond between the 25-OH with Gln305, thus explaining the lower affinity of the mutant proteins for calcitriol. The structure provides the basis for a rational approach to the design of more potent ligands for the treatment of HVDRR.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Calcitriol
/
Receptores de Calcitriol
/
Raquitismo Hipofosfatémico Familiar
/
Mutación
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Steroid Biochem Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Francia