Alanine scanning mutational analysis of the ligand binding pocket of the human Vitamin D receptor |
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Authors: | Yamamoto Keiko Choi Mihwa Abe Daijiro Shimizu Masato Yamada Sachiko |
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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 |
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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. |
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Keywords: | Vitamin D receptor Ligand recognition Alanine scanning mutational analysis 1α ,25-Dihydroxyvitamin D3 Ligand binding Vitamin D |
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