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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 | 2007/04 |
| 形態種別 | 研究論文 |
| 査読 | 査読あり |
| 標題 | Structural basis of D-DOPA oxidation by D-amino acid oxidase: Alternative pathway for dopamine biosynthesis |
| 執筆形態 | その他 |
| 掲載誌名 | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS |
| 出版社・発行元 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| 巻・号・頁 | 355(2),pp.385-391 |
| 著者・共著者 | Tomoya Kawazoe,Hideaki Tsuge,Takahito Imagawa,Kenji Aki,Seiki Kuramitsu,Kiyoshi Fukui |
| 概要 | D-Amino acid oxidase (DAO) degrades the gliotransmitter D-serine, a potent endogenous ligand of N-methyl-D-aspartate type glutamate receptors. It also has been suggested that D-DOPA, the stereoisomer of L-DOPA, is oxidized by DAO and then converted to dopamine via an alternative biosynthetic pathway. Here, we provide direct crystallographic evidence that D-DOPA is readily fitted into the active site of human DAO, where it is oxidized by the enzyme. Moreover, our kinetic data show that the maximal velocity for oxidation of D-DOPA is much greater than for D-serine, which strongly supports the proposed alternative pathway for dopamine biosynthesis in the treatment of Parkinson's disease. In addition, determination of the structures of human DAO in various states revealed that the conformation of the hydrophobic VAAGL stretch (residues 47-51) to be uniquely stable in the human enzyme, which provides a structural basis for the unique kinetic features of human DAO. (c) 2007 Elsevier Inc. All rights reserved. |
| DOI | 10.1016/j.bbrc.2007.01.181 |
| ISSN | 0006-291X |