J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):235-42. Epub 2007 Jan 10.

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

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Département de Biologie et de Génomique Structurales, IGBMC, CNRS/INSERM Université Louis Pasteur, Parc d'innovation BP10142, 67404 Illkirch Cedex, France.

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.

PMID:: 17218092; [PubMed - indexed for MEDLINE]

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Cited by 11 PubMed Central articles

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Structures reported by this article

Crystal Structure Of The Ligand Binding Domain Of The Vitamin D Nuclear Receptor In Complex With Gemini And A Coactivator Peptide

PDB: 2HCD

Source: Danio rerio

Method: X-Ray Diffraction

Resolution: 2.6 Å

See all 2 structures...

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

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