ビタミンD水酸化活性をもつ放線菌由来CYP105A1の立体構造の解明

概要

論文の詳細を見る
Active form of vitamin D_3 plays a crucial role in the maintenance of calcium and phosphorus concentrations in serum. Activation of vitamin D_3 requires 25-hydroxylation by CYP27A1 and CYP2R1 in the liver, and 1α-hydroxylation by CYP27B1 in the kidney. We revealed that Streptomyces griseolus CYP105A1 converts vitamin D_3 into 1α, 25-dihydroxyvitamin D_3 (1α, 25(OH)_2D_3) in spite of its low sequence identity with the mammalian CYPs, and determined the crystal structure of its highly active mutant (R84A) in complex with 1α, 25(OH)_2D_3. Although 1α, 25(OH)_2D_3 is positioned far from the iron atom, a similar binding mode is observed in the structure of the human CYP2R1-VD_3 complex, indicating a common substrate-binding mechanism for 25-hydroxylation. Further mutational analysis of the active site revealed that 25- and 1α-hydroxylation share residues that participate in these reactions. These results provide the structural basis for understanding the mechanism of the two-step hydroxylation that activates vitamin D_3.
日本ビタミン学会の論文
2008-09-25