2E82

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

Summary for 2E82

• Entry DOI: 10.2210/pdb2e82/pdb
• Related: 2DU8 2E48 2E49 2E4A
• Descriptor: D-amino-acid oxidase, FLAVIN-ADENINE DINUCLEOTIDE, (2E)-3-(3,4-DIHYDROXYPHENYL)-2-IMINOPROPANOIC ACID, ... (4 entities in total)
• Functional Keywords: structurally ambivalent peptide, imino-dopa complex, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Peroxisome: P14920
• Total number of polymer chains: 4
• Total formula weight: 162006.53

Authors

Kawazoe, T.,Tsuge, H.,Imagawa, T.,Kuramitsu, S.,Fukui, K. (deposition date: 2007-01-16, release date: 2007-03-06, Last modification date: 2023-10-25)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.7 Å)