Identification of the amino acid residue of CYP27B1 responsible for binding of 25-hydroxyvitamin D3 whose mutation causes vitamin D-dependent rickets type 1

被引:40
作者
Yamamoto, K
Uchida, E
Urushino, N
Sakaki, T
Kagawa, N
Sawada, N
Kamakura, M
Kato, S
Inouye, K
Yamada, S
机构
[1] Toyama Prefectural Univ, Biotechnol Res Ctr, Fac Engn, Toyama 9390398, Japan
[2] Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Chiyoda Ku, Tokyo 1010062, Japan
[3] Tokyo Med & Dent Univ, Sch Biomed Sci, Chiyoda Ku, Tokyo 1010062, Japan
[4] Kyoto Univ, Div Food Sci & Biotechnol, Grad Sch Agr, Sakyo Ku, Kyoto 6068502, Japan
[5] Vanderbilt Univ, Dept Biochem, Sch Med, Nashville, TN 37232 USA
[6] Univ Shizuoka, Lab Endocrinol & Mol Metab, Grad Sch Nutr Sci, Shizuoka 4228526, Japan
[7] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan
关键词
D O I
10.1074/jbc.M505244200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We previously reported the three-dimensional structure of human CYP27B1 (25-hydroxyvitamin D-3 1 alpha-hydroxylase) constructed by homology modeling. Using the three-dimensional model we studied the docking of the substrate, 25-hydroxyvitamin D-3, into the substrate binding pocket of CYP27B1. In this study, we focused on the amino acid residues whose point mutations cause vitamin D-dependent rickets type 1, especially unconserved residues among mitochondrial CYPs such as Gln(65) and Thr(409). Recently, we successfully overexpressed mouse CYP27B1 by using a GroEL/ES co-expression system. In a mutation study of mouse CYP27B1 that included spectroscopic analysis, we concluded that in a 1 alpha-hydroxylation process, Ser(408) of mouse CYP27B1 corresponding to Thr409 of human CYP27B1 forms a hydrogen bond with the 25-hydroxyl group of 25-hydroxyvitamin D-3. This is the first report that shows a critical amino acid residue recognizing the 25-hydroxyl group of the vitamin D-3.
引用
收藏
页码:30511 / 30516
页数:6
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