Adaptability of the Vitamin D nuclear receptor to the synthetic ligand Gemini: remodelling the LBP with one side chain rotation.

Date publication

mars 2007

Auteurs

Membres identifiés du Cancéropôle Est :
Dr MORAS Dino

Tous les auteurs :
Ciesielski F, Rochel N, Moras D

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/17218092

Résumé

The crystal structure of the ligand binding domain (LBD) of the wild-type Vitamin D receptor (VDR) of zebrafish bound to Gemini, a synthetic agonist ligand with two identical side chains branching at carbon 20 reveals a ligand-dependent structural rearrangement of the ligand binding pocket (LBP). The rotation of a Leu side chain opens the access to a channel that can accommodate the second side chain of the ligand. The 25% increase of the LBP's volume does not alter the essential agonist features of VDR. The possibility to adapt the LBP to novel ligands with different chemistry and/or structure opens new perspectives in the design of more specifically targeted ligands.

Référence

J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):235-42