Alanine scanning mutational analysis of the ligand binding pocket of the human Vitamin D receptor.
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.
Yamamoto
Keiko
K
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
Choi
Mihwa
M
Abe
Daijiro
D
Shimizu
Masato
M
Yamada
Sachiko
S
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*
D008024:Ligands; D018167:Receptors, Calcitriol; D000409:Alanine