Adaptability of the Vitamin D nuclear receptor to the synthetic ligand Gemini: remodelling the LBP with one side chain rotation. - Archive ouverte HAL Access content directly
Journal Articles Journal of Steroid Biochemistry and Molecular Biology Year : 2007

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

Abstract

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.

Dates and versions

hal-00190967 , version 1 (23-11-2007)

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Fabrice Ciesielski, Natacha Rochel, Dino Moras. Adaptability of the Vitamin D nuclear receptor to the synthetic ligand Gemini: remodelling the LBP with one side chain rotation.. Journal of Steroid Biochemistry and Molecular Biology, 2007, 103 (3-5), pp.235-42. ⟨10.1016/j.jsbmb.2006.12.003⟩. ⟨hal-00190967⟩
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