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ツゲ ヒデアキ
TSUGE HIDEAKI
津下 英明 所属 京都産業大学 生命科学部 先端生命科学科 職種 教授 |
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| 言語種別 | 英語 |
| 発行・発表の年月 | 2007 |
| 形態種別 | 研究論文 |
| 標題 | Human D-amino acid oxidase: an update and review |
| 執筆形態 | その他 |
| 掲載誌名 | CHEMICAL RECORD |
| 出版社・発行元 | JOHN WILEY & SONS INC |
| 巻・号・頁 | 7(5),pp.305-315 |
| 著者・共著者 | Tomoya Kawazoe,Hwan Ki Park,Sanae Iwana,Hideaki Tsuge,Kiyoshi Fukui |
| 概要 | The flavoprotein D-amino acid oxidase (DAO) degrades the gliotransmitter D-Ser, a potent activator of N-methyl-D-aspartate-type glutamate receptors. A body of evidence suggests that DAO, together with its activator, G72 protein, may play a key role in the pathophysiology of schizophrenia. It has also been suggested that 3,4-dihydroxy-D-phenylalanine (D-DOPA), the stereoisomer of 3,4-dihydroxy-L-phenylalanine (L-DOPA), is oxidized by DAO and converted to dopamine via an alternative biosynthetic pathway. We determined the crystal structures of human DAO in complex with the reaction products of two clinically important substrates, D-Ser and D-DOPA. Kinetic data show that the maximum velocity is much greater for D-DOPA than that for D-Ser, which strongly supports the proposed alternative pathway for dopamine biosynthesis in the treatment of Parkinson's disease. In addition, biochemical characterization of human DAO indicates that it binds FAD more weakly than does porcine D-amino acid oxidase (pDAO) and exists as a stable homodimer, even in the apoprotein form. Determination of the structures of human DAO) in various states reveals that, in contrast to pDAO, the hydrophobic-Val-Ala-Ala-Gly Leu (VAAGL) stretch (residues 47-51, structurally ambivalent peptide) located at the si-face of the flavin ring assumes a uniquely stable conformation, which provides a structural basis for the unique kinetic features of human DAO. |
| DOI | 10.1002/tcr.20129 |
| ISSN | 1527-8999 |