ビタミンD 代謝酵素の構造と機能に関する研究

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タイトル別名
  • Structure-function analysis of vitamin D metabolizing enzymes
  • ビタミン D タイシャ コウソ ノ コウゾウ ト キノウ ニ カンスル ケンキュウ

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説明

We have successfully expressed four cytochromes P450 (CYP27A1, CYP27B1, CYP24A1, and CYP2R1), which play important roles in the metabolism of vitamin D in mammals, E. coli or S. cerevisiae cells, and have revealed their enzymatic properties. The analysis of missense mutants of CYP27B1, which cause rickets type I, identified amino acid residues that play important roles in the function of CYP27B1 such as substrate binding, activation of molecular oxygen, interaction with the electron donor (adrenodoxin), heme binding, and folding of the P450 structure. We have revealed the metabolic pathways of a lot of promising vitamin D analogs for clinical uses. These studies suggested the importance of their resistance to CYP24A1-dependent catabolism. We have succeeded in the determination of the tertiary structure of vitamin D hydroxylase (CYP105A1) derived from Actinomycetes and have dramatically enhanced its activity by substitution of two amino acids in its protein based on its tertiary structure. The recombinant actinomycetes expressing the CYP105A1 variant have the possibility of their practical application to produce the active forms of vitamin D. Recently, we focus on the elucidation of the metabolism and action mechanism of vitamin D using genetically modified mice and rats.

収録刊行物

  • ビタミン

    ビタミン 93 (11), 469-477, 2019-11-25

    公益社団法人 日本ビタミン学会

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