2E82

Crystal structure of human D-amino acid oxidase complexed with imino-DOPA

2E82 の概要

• エントリーDOI: 10.2210/pdb2e82/pdb
• 関連するPDBエントリー: 2DU8 2E48 2E49 2E4A
• 分子名称: D-amino-acid oxidase, FLAVIN-ADENINE DINUCLEOTIDE, (2E)-3-(3,4-DIHYDROXYPHENYL)-2-IMINOPROPANOIC ACID, ... (4 entities in total)
• 機能のキーワード: structurally ambivalent peptide, imino-dopa complex, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Peroxisome: P14920
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 162006.53

構造登録者

Kawazoe, T.,Tsuge, H.,Imagawa, T.,Kuramitsu, S.,Fukui, K. (登録日: 2007-01-16, 公開日: 2007-03-06, 最終更新日: 2023-10-25)

主引用文献

Kawazoe, T.,Tsuge, H.,Imagawa, T.,Aki, K.,Kuramitsu, S.,Fukui, K.
Structural basis of d-DOPA oxidation by d-amino acid oxidase: Alternative pathway for dopamine biosynthesis.
Biochem.Biophys.Res.Commun., 355:385-391, 2007

PubMed Abstract: 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.

PubMed: 17303072
DOI: 10.1016/j.bbrc.2007.01.181

実験手法

X-RAY DIFFRACTION (2.7 Å)