Yamamoto Keiko, Choi Mihwa, Abe Daijiro, Shimizu Masato, Yamada Sachiko
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):282-5. doi: 10.1016/j.jsbmb.2006.12.018. Epub 2007 Jan 16.
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.
我们对维生素D受体配体结合口袋周围的氨基酸残基进行了全面的丙氨酸扫描突变分析，以研究受体识别配体的机制。这是核受体超家族中的首次全面分析。我们的结果证明了配体结合口袋周围所有残基的作用和重要性。此外，该分析表明了配体特异性的配体-蛋白质相互作用，这在确定各个配体的反式激活能力方面具有关键重要性。因此，使用1β-甲基-1α,25-二羟基维生素D(3)的分析揭示了1β-甲基基团与受体之间的特定范德华相互作用。
