title: Alanine scanning mutational analysis of the ligand binding pocket of the human Vitamin D receptor.
abstract: We achieved exhaustive alanine scanning mutational analysis of the amino acid residues lining the ligand binding pocket of the Vitamin D receptor to investigate the mechanism of the ligand recognition by the receptor. This is the first exhaustive analysis in the nuclear receptor superfamily. Our results demonstrated the role and importance of all the residues lining the ligand binding pocket. In addition, this analysis was found to indicate ligand-specific ligand-protein interactions, which have key importance in determining the transactivation potency of the individual ligands. Thus, the analysis using 1beta-methyl-1alpha,25-dihydroxyvitamin D(3) revealed the specific van der Waals interactions of 1beta-methyl group with the receptor.
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan. yamamoto.mr@tmd.ac.jp
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Mihwa
authors.initials: M
authors.lastname: Choi
authors.forename: Daijiro
authors.initials: D
authors.lastname: Abe
authors.forename: Masato
authors.initials: M
authors.lastname: Shimizu
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000409:Alanine / Q000235:genetics* / Q000378:metabolism*; D001665:Binding Sites; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism*
chemical_list: D008024:Ligands; D018167:Receptors, Calcitriol; D000409:Alanine