Three-dimensional modeling of and ligand docking to vitamin D receptor ligand binding domain
AUTOR(ES)
Yamamoto, Keiko
FONTE
The National Academy of Sciences
RESUMO
The ligand binding domain of the human vitamin D receptor (VDR) was modeled based on the crystal structure of the retinoic acid receptor. The ligand binding pocket of our VDR model is spacious at the helix 11 site and confined at the β-turn site. The ligand 1α,25-dihydroxyvitamin D3 was assumed to be anchored in the ligand binding pocket with its side chain heading to helix 11 (site 2) and the A-ring toward the β-turn (site 1). Three residues forming hydrogen bonds with the functionally important 1α- and 25-hydroxyl groups of 1α,25-dihydroxyvitamin D3 were identified and confirmed by mutational analysis: the 1α-hydroxyl group is forming pincer-type hydrogen bonds with S237 and R274 and the 25-hydroxyl group is interacting with H397. Docking potential for various ligands to the VDR model was examined, and the results are in good agreement with our previous three-dimensional structure-function theory.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=26457Documentos Relacionados
- Three-dimensional numerical modeling of RTM and LRTM processes
- Three-dimensional structure of poliovirus receptor bound to poliovirus
- Design of three-dimensional domain-swapped dimers and fibrous oligomers
- The three-dimensional structure of retinol-binding protein.
- CDD: a database of conserved domain alignments with links to domain three-dimensional structure
