PUBLICATION
Adaptability of the Vitamin D nuclear receptor to the synthetic ligand Gemini: Remodelling the LBP with one side chain rotation
- Authors
- Ciesielski, F., Rochel, N., and Moras, D.
- ID
- ZDB-PUB-070122-36
- Date
- 2007
- Source
- The Journal of steroid biochemistry and molecular biology 103(3-5): 235-242 (Journal)
- Registered Authors
- Keywords
- 1α,25(OH)2D3, Gemini, Vitamin D receptor, Crystal structure, Adaptability
- MeSH Terms
-
- Crystallography, X-Ray
- Mutation/genetics
- Humans
- Binding Sites
- Calcitriol/analogs & derivatives*
- Calcitriol/metabolism
- Adaptation, Biological*
- Protein Binding
- Rats
- Animals
- Receptors, Calcitriol/chemistry*
- Receptors, Calcitriol/genetics
- Receptors, Calcitriol/metabolism*
- Ligands
- Models, Molecular
- Cell Nucleus/metabolism*
- Zebrafish
- Protein Structure, Tertiary
- PubMed
- 17218092 Full text @ Steroid Biochem. Mol. Biol.
Citation
Ciesielski, F., Rochel, N., and Moras, D. (2007) Adaptability of the Vitamin D nuclear receptor to the synthetic ligand Gemini: Remodelling the LBP with one side chain rotation. The Journal of steroid biochemistry and molecular biology. 103(3-5):235-242.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping