Three-dimensional modeling of and ligand docking to vitamin D receptor ligand binding domain
| Autor: | Wanda Sicinska, Hiroshi Ooizumi, Kazuhiko Umesono, Hiroyuki Masuno, Keiko Yamamoto, Tetsuya Taga, Kinichi Nakashima, Hector F. DeLuca, Mihwa Choi, Sachiko Yamada, Janeen L. Vanhooke |
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| Rok vydání: | 2000 |
| Předmět: |
Models
Molecular Transcription Genetic Receptors Retinoic Acid Stereochemistry Molecular Sequence Data Plasma protein binding Ligands Calcitriol receptor Protein Structure Secondary Structure-Activity Relationship Protein structure Calcitriol Animals Humans Computer Simulation Amino Acid Sequence Peptide sequence Multidisciplinary Chemistry Hydrogen bond Hydrogen Bonding Biological Sciences Ligand (biochemistry) Retinoic acid receptor Docking (molecular) COS Cells Mutation Receptors Calcitriol Sequence Alignment Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences. 97:1467-1472 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.020522697 |
| Popis: | 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 D 3 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 D 3 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. |
| Databáze: | OpenAIRE |
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