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Oxidoreductase
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PDB id
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2e48
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Contents |
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* Residue conservation analysis
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PDB id:
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Oxidoreductase
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Title:
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Crystal structure of human d-amino acid oxidase: substrate- free holoenzyme
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Structure:
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D-amino-acid oxidase. Chain: a, b, c, d. Synonym: damox, dao, daao. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
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Resolution:
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2.90Å
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R-factor:
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0.213
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R-free:
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0.259
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Authors:
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T.Kawazoe,H.Tsuge,T.Imagawa,K.Fukui
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Key ref:
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T.Kawazoe
et al.
(2007).
Structural basis of D-DOPA oxidation by D-amino acid oxidase: alternative pathway for dopamine biosynthesis.
Biochem Biophys Res Commun,
355,
385-391.
PubMed id:
DOI:
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Date:
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05-Dec-06
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Release date:
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06-Mar-07
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PROCHECK
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Headers
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References
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P14920
(OXDA_HUMAN) -
D-amino-acid oxidase
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Seq:
Struc:
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347 a.a.
340 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.1.4.3.3
- D-amino-acid oxidase.
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Pathway:
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Cephalosporin Biosynthesis
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Reaction:
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A D-amino acid + H2O + O2 = a 2-oxo acid + NH3 + H2O2
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D-amino acid
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+
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H(2)O
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+
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O(2)
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=
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2-oxo acid
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+
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NH(3)
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+
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H(2)O(2)
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Cofactor:
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FAD
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FAD
Bound ligand (Het Group name =
FAD)
corresponds exactly
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Gene Ontology (GO) functional annotation
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Cellular component
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peroxisome
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2 terms
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Biological process
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oxidation-reduction process
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4 terms
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Biochemical function
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nucleotide binding
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4 terms
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DOI no:
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Biochem Biophys Res Commun
355:385-391
(2007)
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PubMed id:
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Structural basis of D-DOPA oxidation by D-amino acid oxidase: alternative pathway for dopamine biosynthesis.
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T.Kawazoe,
H.Tsuge,
T.Imagawa,
K.Aki,
S.Kuramitsu,
K.Fukui.
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ABSTRACT
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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.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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M.Katane,
Y.Saitoh,
K.Maeda,
T.Hanai,
M.Sekine,
T.Furuchi,
and
H.Homma
(2011).
Role of the active site residues arginine-216 and arginine-237 in the substrate specificity of mammalian D-aspartate oxidase.
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Amino Acids, 40,
467-476.
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L.Pollegioni,
and
S.Sacchi
(2010).
Metabolism of the neuromodulator D-serine.
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Cell Mol Life Sci, 67,
2387-2404.
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L.Verrall,
P.W.Burnet,
J.F.Betts,
and
P.J.Harrison
(2010).
The neurobiology of D-amino acid oxidase and its involvement in schizophrenia.
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Mol Psychiatry, 15,
122-137.
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M.Katane,
Y.Saitoh,
Y.Seida,
M.Sekine,
T.Furuchi,
and
H.Homma
(2010).
Comparative characterization of three D-aspartate oxidases and one D-amino acid oxidase from Caenorhabditis elegans.
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Chem Biodivers, 7,
1424-1434.
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K.Ono,
Y.Shishido,
H.K.Park,
T.Kawazoe,
S.Iwana,
S.P.Chung,
R.M.Abou El-Magd,
K.Yorita,
M.Okano,
T.Watanabe,
N.Sano,
Y.Bando,
K.Arima,
T.Sakai,
and
K.Fukui
(2009).
Potential pathophysiological role of D-amino acid oxidase in schizophrenia: immunohistochemical and in situ hybridization study of the expression in human and rat brain.
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J Neural Transm, 116,
1335-1347.
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L.Verrall,
M.Walker,
N.Rawlings,
I.Benzel,
J.N.Kew,
P.J.Harrison,
and
P.W.Burnet
(2007).
d-Amino acid oxidase and serine racemase in human brain: normal distribution and altered expression in schizophrenia.
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Eur J Neurosci, 26,
1657-1669.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
