Any feedback?
Information on EC 1.4.3.3 - D-amino-acid oxidase and Organism(s) Homo sapiens and UniProt Accession P14920
for references in articles please use BRENDA:EC1.4.3.3Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.4.3.3 D-amino-acid oxidaseIUBMB Comments
A flavoprotein (FAD). Wide specificity for D-amino acids. Also acts on glycine.
Specify your search results
Word Map
- 1.4.3.3
- d-serine
-
schizophrenia
- peroxisomal
- flavin
- n-methyl-d-aspartate
- d-alanine
- catalase
- fad
- nmda
-
deamination
- benzoate
-
flavoenzyme
- flavoproteins
- racemase
- variabilis
-
l-amino
-
neurotransmission
- d-aspartate
- gracilis
-
co-agonist
- rhodotorula
- cephalosporin
-
glutamatergic
- urate
- d-proline
- d-ala
- d-ser
-
imino
-
antipsychotic
-
hypofunction
- d-methionine
- isoalloxazine
- acylase
-
fad-containing
- toruloides
- rhodosporidium
- d-glutamate
-
fad-dependent
- d-cysteine
-
kynurenic
- sulfurtransferase
- d-valine
- synthesis
- medicine
- d-leucine
- cerium
-
7-aminocephalosporanic
- d-tryptophan
- d-phenylalanine
- neuregulin
- 3-mercaptopyruvate
- sarcosine
- industry
- biotechnology
- analysis
- diagnostics
- drug development
- pharmacology
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
d-amino acid oxidase, d-amino-acid oxidase, hdaao, d-aao, rgdaao, tvdao, tvdaao, d-aminoacid oxidase, peg-dao, pkdaao, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
D-amino acid oxidase
-
-
D-aminoacid oxidase
-
-
-
-
DAAO
DAMOX
-
-
-
-
DAO
ophio-amino-acid oxidase
-
-
-
-
oxidase, D-amino acid
-
-
-
-
DAAO
-
-
-
-
DAAO
-
-
DAO
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
oxidative deamination
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
-
-, -
SYSTEMATIC NAME
IUBMB Comments
D-amino-acid:oxygen oxidoreductase (deaminating)
A flavoprotein (FAD). Wide specificity for D-amino acids. Also acts on glycine.
CAS REGISTRY NUMBER
COMMENTARY
9000-88-8
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
D-DOPA + H2O + O2
3,4-dihydroxyphenylpyruvic acid + NH3 + H2O2
the maximal velocity for oxidation of D-DOPA is much greater than for D-serine
-
-
?
N-methyl-D-aspartate + H2O + O2
oxaloacetate + methylamine + H2O2
-
-
-
?
3,4-dihydroxy-D-phenylalanine + H2O + O2
3,4-dihydroxyphenylpyruvate + NH3 + H2O2
-
-
-
-
?
D-Ala + H2O + O2
pyruvate + NH3 + H2O2
-
-
-
-
?
D-alanine + H2O + O2
pyruvate + NH3 + H2O2
-
-
-
-
?
D-Ser + H2O + O2
2-oxo-3-hydroxypropionate + NH3 + H2O2
-
-
-
-
?
D-serine + H2O + O2
2-oxo-3-hydroxypropionic acid + NH3 + H2O2
-
-
-
-
?
cephalosporin C + H2O + O2
7-(5-oxoadipoamido)cephalosporanic acid + NH3 + H2O2
-
-
-
?
cephalosporin C + H2O + O2
7-(5-oxoadipoamido)cephalosporanic acid + NH3 + H2O2
-
-
-
-
?
D-cysteine + H2O + O2
2-oxo-3-sulfanylpropionate + NH3 + H2O2
-
-
-
?
D-serine + H2O + O2
2-oxo-3-hydroxypropionate + NH3 + H2O2
-
-
-
?
D-serine + H2O + O2
2-oxo-3-hydroxypropionate + NH3 + H2O2
-
-
-
?
D-serine + H2O + O2
2-oxo-3-hydroxypropionate + NH3 + H2O2
the apoprotein form of hDAAO binds the substrate D-serine, which increases FAD binding thus increasing the amount of active holoenzyme in solution
-
-
?
D-serine + H2O + O2
2-oxo-3-hydroxypropionic acid + NH3 + H2O2
-
-
-
?
D-serine + H2O + O2
2-oxo-3-hydroxypropionate + NH3 + H2O2
-
-
-
-
?
D-serine + H2O + O2
2-oxo-3-hydroxypropionate + NH3 + H2O2
-
D-serine, an endogenous agonist of the N-methyl-D-aspartate, NMDA, receptors, is effective in the treatment of schizophrenia. However, orally administered D-serine is metabolized substantially by D-amino acid oxidase diminishing its oral bioavailability
-
-
?
D-serine + H2O + O2
2-oxo-3-hydroxypropionate + NH3 + H2O2
-
metabolizaation of the N-methyl D-aspartate receptor co-agonist
-
-
?
D-serine + H2O + O2
2-oxo-3-hydroxypropionate + NH3 + H2O2
-
low catalytic efficiency and substrate affinity on the physiological substrate D-serine
-
-
?
D-tryptophan + H2O + O2
indole-3-pyruvic acid + NH3 + H2O2
-
DAAO catalyzes the production of aryl hydrocarbon receptor, AHR, agonists through the enzymatic conversion of D-tryptophan to indole-3-pyruvic acid
-
-
?
additional information
?
-
D-aspartate and D-glutamate are no substrates
-
-
?
additional information
?
-
-
D-aspartate and D-glutamate are no substrates
-
-
?
additional information
?
-
DAAO interacts with its physiological partner pLG72, the interaction is not inhibited by benzoate and chlorpromazine
-
-
?
additional information
?
-
-
DAAO interacts with its physiological partner pLG72, the interaction is not inhibited by benzoate and chlorpromazine
-
-
?
additional information
?
-
comparison of the kinetics of trypsin cleavage of hDAAO in the presence of various ligands, overview
-
-
?
additional information
?
-
-
comparison of the kinetics of trypsin cleavage of hDAAO in the presence of various ligands, overview
-
-
?
additional information
?
-
DAAO is mainly active on neutral, hydrophobic and slightly polar D-amino acids and shows a preference for aromatic amino acids
-
-
-
additional information
?
-
-
DAAO is mainly active on neutral, hydrophobic and slightly polar D-amino acids and shows a preference for aromatic amino acids
-
-
-
additional information
?
-
-
DAAO is a catabolic flavoenzyme that catalyzes the oxidative deamination of D-amino acids to the corresponding a-keto acids, hydrogen peroxide, and ammonia. DAAO is strictly specific for D-isomers of amino acids
-
-
?
additional information
?
-
-
the mechanism of the enzyme regulation is complex and multi-parametric because the same enzyme simultaneously influences the level of different D-amino acids, which can result in opposing effects, overview
-
-
?
additional information
?
-
-
D-amino acid oxidase is a flavoenzyme that catalyzes the oxidation of D-amino acids to the corresponding imino acids and hydrogen peroxide
-
-
?
additional information
?
-
-
hDAAO exhibits optimal activity toward neutral D-amino acids and marginal activity toward basic ones, while acidic D-amino acids are not oxidized, structure-function relationship analysis, overview
-
-
?
additional information
?
-
-
the enzyme catalyzes oxidative deamination of D-amino acids yielding hydrogen peroxide and an imino acid. The latter is further non-enzymatically hydrolyzed to an alpha-keto acid and ammonium. DAAO is highly specific towards D-isomers of amino acids, it is almost inactive towards the corresponding L-isomer
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
D-serine + H2O + O2
2-oxo-3-hydroxypropionate + NH3 + H2O2
the apoprotein form of hDAAO binds the substrate D-serine, which increases FAD binding thus increasing the amount of active holoenzyme in solution
-
-
?
D-Ser + H2O + O2
2-oxo-3-hydroxypropionate + NH3 + H2O2
-
-
-
-
?
D-tryptophan + H2O + O2
indole-3-pyruvic acid + NH3 + H2O2
-
DAAO catalyzes the production of aryl hydrocarbon receptor, AHR, agonists through the enzymatic conversion of D-tryptophan to indole-3-pyruvic acid
-
-
?
D-serine + H2O + O2
2-oxo-3-hydroxypropionate + NH3 + H2O2
-
-
-
-
?
D-serine + H2O + O2
2-oxo-3-hydroxypropionate + NH3 + H2O2
-
D-serine, an endogenous agonist of the N-methyl-D-aspartate, NMDA, receptors, is effective in the treatment of schizophrenia. However, orally administered D-serine is metabolized substantially by D-amino acid oxidase diminishing its oral bioavailability
-
-
?
D-serine + H2O + O2
2-oxo-3-hydroxypropionate + NH3 + H2O2
-
metabolizaation of the N-methyl D-aspartate receptor co-agonist
-
-
?
D-serine + H2O + O2
2-oxo-3-hydroxypropionate + NH3 + H2O2
-
low catalytic efficiency and substrate affinity on the physiological substrate D-serine
-
-
?
additional information
?
-
DAAO interacts with its physiological partner pLG72, the interaction is not inhibited by benzoate and chlorpromazine
-
-
?
additional information
?
-
-
DAAO interacts with its physiological partner pLG72, the interaction is not inhibited by benzoate and chlorpromazine
-
-
?
additional information
?
-
-
DAAO is a catabolic flavoenzyme that catalyzes the oxidative deamination of D-amino acids to the corresponding a-keto acids, hydrogen peroxide, and ammonia. DAAO is strictly specific for D-isomers of amino acids
-
-
?
additional information
?
-
-
the mechanism of the enzyme regulation is complex and multi-parametric because the same enzyme simultaneously influences the level of different D-amino acids, which can result in opposing effects, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FAD
the apoprotein form of hDAAO binds the substrate D-serine, this interaction increases FAD binding thus increasing the amount of active holoenzyme in solution, binding analysis of FAD, overview
FAD
Kd value 0.008 mM for FAD-apoprotein complex. Benzoate binding favors a protein conformation with a higher affinity for the cofactor FAD
FAD
R120E and R120L variants show absorbance maxima at 448, 384, and 279 nm and an Abs279nm/Abs448nm ratio of 10.4 and 11.2, respectively, which are close to the value of 10.6 reported for the wild-type enzyme
FAD
-
-
FAD
-
human enzyme weakly binds FAD and shows a significantly slower rate of flavin reduction compared to porcine enzyme
FAD
-
the enzyme contains one molecule of non-covalently bound FAD per protein monomer, which can be easily isolated from the apoprotein by dialysis in the presence of 1 M KBr
FAD
-
flavoenzyme, weak interaction with the flavin cofactor in the free form,the cofactor binding is significantly tighter in the presence of an active site ligand. hDAAO exists as an equilibrium of holo- and apoprotein forms in solution
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
divalent ions and nucleotides do not affect enzyme function
additional information
-
divalent ions and nucleotides do not affect enzyme function
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
([4-[(3,4-dichloro-5-methyl-1H-pyrrole-2-carbonyl)amino]-1H-pyrrole-2-carbonyl]amino)acetic acid
100% inhibition at 0.02 mM
-
([4-[(4,5-dibromo-1H-pyrrole-2-carbonyl)amino]-1H-pyrrole-2-carbonyl]amino)acetic acid
100% inhibition at 0.02 mM
-
([4-[(4,5-dichloro-1H-pyrrole-2-carbonyl)amino]-1H-pyrrole-2-carbonyl]amino)acetic acid
100% inhibition at 0.02 mM
-
([4-[(4-bromo-1H-pyrrole-2-carbonyl)amino]-1H-pyrrole-2-carbonyl]amino)acetic acid
100% inhibition at 0.02 mM
-
4-bromo-3-nitrobenzoate
there are two binding pockets of DAO to its inhibitor 4-bromo-3-nitrobenzoate, one is shared with substrate D-Ser and FAD, and the other is an cleft between the subunits of a DAO dimer
-
4-hydroxy-6-[2-(7-hydroxy-2-oxo-4-phenyl-2H-1-benzopyran-6-yl)ethyl]pyridazin-3(2H)-one
-
-
4-hydroxy-6-[2-[7-hydroxy-4-(3-methoxyphenyl)-2-oxo-2H-1-benzopyran-6-yl]ethyl]pyridazin-3(2H)-one
-
-
4-hydroxy-6-[2-[7-hydroxy-4-(3-methylphenyl)-2-oxo-2H-1-benzopyran-6-yl]ethyl]pyridazin-3(2H)-one
-
-
4-hydroxy-6-[2-[7-hydroxy-4-(4-methylphenyl)-2-oxo-2H-1-benzopyran-6-yl]ethyl]pyridazin-3(2H)-one
-
-
5-methylpyrazole-3-carboxylic acid
AS057278, selective D-amino acid oxidase inhibitor
6-[2-[4-(3-chlorophenyl)-7-hydroxy-2-oxo-2H-1-benzopyran-6-yl]ethyl]-4-hydroxypyridazin-3(2H)-one
-
-
6-[2-[4-(4-chlorophenyl)-7-hydroxy-2-oxo-2H-1-benzopyran-6-yl]ethyl]-4-hydroxypyridazin-3(2H)-one
-
-
[[4-[(4,5-dibromo-1H-pyrrole-2-carbonyl)amino]-1H-pyrrole-2-carbonyl](methyl)amino]acetic acid
100% inhibition at 0.02 mM
-
3-[[(2H-1,3-benzodioxol-5-yl)methyl]sulfanyl]-5-hydroxy-1,2,4-triazin-6(1H)-one
-
-
3-[[(6-fluoronaphthalen-2-yl)methyl]sulfanyl]-5-hydroxy-1,2,4-triazin-6(1H)-one
-
-
3-[[([1,1'-biphenyl]-3-yl)methyl]sulfanyl]-5-hydroxy-1,2,4-triazin-6(1H)-one
-
-
3-[[([1,1'-biphenyl]-4-yl)methyl]sulfanyl]-5-hydroxy-1,2,4-triazin-6(1H)-one
-
-
4H-thieno [3,2-b]pyrrole-5-carboxylic acid
-
i.e. compound 8, a moderately potent inhibitor of human DAAO in vitro
4H-thieno[3,2-b] pyrrole-5-carboxylic acid
-
i.e. compound 8, very specific inhibitor of DAAO
6-hydroxy-2-[2-(1H-pyrrolo[2,3-b]pyridin-1-yl)ethyl]-1,2,4-triazine-3,5(2H,4H)-dione
-
-
Sodium benzoate
-
inhibits the enzyme activity by by impeding the interaction of the enzyme with the flavin prosthetic group
6-chlorobenzo[d]isoxazol-3-ol
a decrease in protein fluorescence is observed at increasing 6-chlorobenzo[d]isoxazol-3-ol concentrations
benzoate
a classical substrate-competitive inhibitor, effect of benzoate on the FAD-binding process to hDAAO apoprotein
benzoate
a decrease in protein fluorescence is observed at increasing concentrations, with a biphasic change
additional information
benzoate and CPZ similarly modify the short-term cellular D-serine concentration but affect the cellular concentration of hDAAO differently
-
additional information
-
benzoate and CPZ similarly modify the short-term cellular D-serine concentration but affect the cellular concentration of hDAAO differently
-
additional information
identification of inhibitors by a structure based virtual screening campaign based on the X-ray structures of DAAO complexes where larger ligands shift the loop (lid opening) covering the native binding site followed by the in vitro test. Compounds bind to the active site with a salt-bridge. Displacement of and interaction with the loop covering the active site contributes significantly to the activity of the most potent compounds
-
additional information
not inhibitory: N-acetyl-cysteine at 10 mM. No change in protein fluorescence is observed with glycine (up to 50mM), ATP (up to 20mM), NMDA (up to 50mM), or D-glutamate (up to 50mM)
-
additional information
-
not inhibitory: N-acetyl-cysteine at 10 mM. No change in protein fluorescence is observed with glycine (up to 50mM), ATP (up to 20mM), NMDA (up to 50mM), or D-glutamate (up to 50mM)
-
additional information
synthesis of inhibitors that interact with loop 218-224 at the top of the binding pocket and open the lid over the active site of DAAO. The DAAO inhibitors show low nanomolar activity and low sensitivity to the substituents investigated. The interactions of the linker connecting the pendant aromatic moiety and the acidic headgroup with the enzyme are crucial for achieving significant inhibitory activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
D-amino acid oxidase activator
-
i.e. DAOA or G72, the gene encoding the activator is located on chromosome 13q32-34
-
pLG72
-
i.e. DAOA or D-amino acid oxidase activator, interacts with and activates the enzyme, genotyping in healthy persons and schizophrenia patients, overview
-
additional information
-
mean DAAOactivity is 2fold higher in the schizophrenia patients group compared with the control group
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
DAAO-lingand interaction kinetics, overview
-
additional information
additional information
-
DAAO-lingand interaction kinetics, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00019
3-(2-phenylethyl)-4H-furo[3,2-b]pyrrole-5-carboxylic acid
pH and temperature not specified in the publication
0.000013
3-hydroxy-2H-1-benzopyran-2-one
pH and temperature not specified in the publication
0.0000072
4-[2-(4-chlorophenyl)ethyl]-1H-pyrrole-2-carboxylic acid
pH and temperature not specified in the publication
0.0000035
4H-thieno[3,2-b]pyrrole-5-carboxylic acid
pH and temperature not specified in the publication
0.0000017
5,6-dichloro-1,2-benzoxazol-3-ol
pH and temperature not specified in the publication
additional information
additional information
-
inhibition kinetics with risperidone, in vivo inhibition of cellular DAO activity in LLC-PK1 cells and cytotoxicity, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0088
([4-[(3,4-dichloro-5-methyl-1H-pyrrole-2-carbonyl)amino]-1H-pyrrole-2-carbonyl]amino)acetic acid
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.00039
([4-[(4,5-dibromo-1H-pyrrole-2-carbonyl)amino]-1H-pyrrole-2-carbonyl]amino)acetic acid
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.0052
([4-[(4,5-dichloro-1H-pyrrole-2-carbonyl)amino]-1H-pyrrole-2-carbonyl]amino)acetic acid
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.0067
([4-[(4-bromo-1H-pyrrole-2-carbonyl)amino]-1H-pyrrole-2-carbonyl]amino)acetic acid
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.005
1,4-dihydropyrrolo[3,2-c]pyrazole-5-carboxylic acid
Homo sapiens
IC50 above 0.005 mM
0.005
2,3-dimethyl-4H-furo[3,2-b]pyrrole-5-carboxylic acid
Homo sapiens
IC50 above 0.005 mM
0.005
2-(2,4-dichlorophenyl)-4H-furo[3,2-b]pyrrole-5-carboxylic acid
Homo sapiens
IC50 above 0.005 mM
0.005
2-(3-chlorophenyl)-4H-furo[3,2-b]pyrrole-5-carboxylic acid
Homo sapiens
IC50 above 0.005 mM
0.005
2-(4-chlorophenyl)-4H-furo[3,2-b]pyrrole-5-carboxylic acid
Homo sapiens
IC50 above 0.005 mM
0.005
2-chloro-4H-furo[3,2-b]pyrrole-5-carboxylic acid
Homo sapiens
IC50 above 0.005 mM
0.005
2-chloro-4H-thieno[3,2-b]pyrrole-5-carboxylic acid
Homo sapiens
IC50 above 0.005 mM
0.005
2-phenyl-4H-furo[3,2-b]pyrrole-5-carboxylic acid
Homo sapiens
IC50 above 0.005 mM
0.0005
2-[(3,4-dichlorophenoxy)methyl]-5-hydroxy-4H-pyran-4-one
Homo sapiens
pH and temperature not specified in the publication
0.0007
2-[(4-chlorophenoxy)methyl]-5-hydroxy-4H-pyran-4-one
Homo sapiens
pH and temperature not specified in the publication
0.0008
2-[(4-fluorophenoxy)methyl]-5-hydroxy-4H-pyran-4-one
Homo sapiens
pH and temperature not specified in the publication
0.02
2-[(benzyloxy)methyl]-5-hydroxy-4H-pyran-4-one
Homo sapiens
pH and temperature not specified in the publication
0.00036
2-[[(1Z)-1-chloroprop-1-en-1-yl]sulfanyl]prop-2-enoic acid
Homo sapiens
pH 8.5, 23°C
-
0.0001
2-[[(3,4-dichlorophenyl)sulfanyl]methyl]-5-hydroxy-4H-pyran-4-one
Homo sapiens
pH and temperature not specified in the publication
0.0002
2-[[(4-chlorophenyl)sulfanyl]methyl]-5-hydroxy-4H-pyran-4-one
Homo sapiens
pH and temperature not specified in the publication
0.0003
2-[[(4-fluorophenyl)sulfanyl]methyl]-5-hydroxy-4H-pyran-4-one
Homo sapiens
pH and temperature not specified in the publication
0.005
3-(3-chlorophenyl)-4H-furo[3,2-b]pyrrole-5-carboxylic acid
Homo sapiens
IC50 above 0.005 mM
0.005
3-(4-chlorophenyl)-4H-furo[3,2-b]pyrrole-5-carboxylic acid
Homo sapiens
IC50 above 0.005 mM
0.005
3-(hydroxymethyl)-4H-furo[3,2-b]pyrrole-5-carboxylic acid
Homo sapiens
IC50 above 0.005 mM
0.000128
3-hydroxy-1,5-naphthyridin-2(1H)-one hydrobromide
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.000032
3-hydroxy-1,6-naphthyridin-2(1H)-one hydrobromide
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.000784
3-hydroxy-1,7-naphthyridin-2(1H)-one hydrobromide
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.0173
3-hydroxy-4-methylquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.000016
3-hydroxy-5-methylquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.00275
3-hydroxy-6-methylquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.000197
3-hydroxy-7-methylquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.000038
3-hydroxy-8-methylquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.000004
3-hydroxyquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.005
3-pyridin-3-yl-4H-furo[3,2-b]pyrrole-5-carboxylic acid
Homo sapiens
IC50 above 0.005 mM
0.000112
4-hydroxy-6-[2-(7-hydroxy-2-oxo-4-phenyl-2H-1-benzopyran-6-yl)ethyl]pyridazin-3(2H)-one
Homo sapiens
pH 8, 37°C
-
0.000073
4-hydroxy-6-[2-[7-hydroxy-4-(3-methoxyphenyl)-2-oxo-2H-1-benzopyran-6-yl]ethyl]pyridazin-3(2H)-one
Homo sapiens
pH 8, 37°C
-
0.000052
4-hydroxy-6-[2-[7-hydroxy-4-(3-methylphenyl)-2-oxo-2H-1-benzopyran-6-yl]ethyl]pyridazin-3(2H)-one
Homo sapiens
pH 8, 37°C
-
0.000474
4-hydroxy-6-[2-[7-hydroxy-4-(4-methylphenyl)-2-oxo-2H-1-benzopyran-6-yl]ethyl]pyridazin-3(2H)-one
Homo sapiens
pH 8, 37°C
-
0.005
4H-pyrrolo[2,3-d][1,3]oxazole-5-carboxylic acid
Homo sapiens
IC50 above 0.005 mM
0.000004
5-chloro-3-hydroxyquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.000003
5-chloro-6-fluoro-3-hydroxy-1,8-naphthyridin-2(1H)-one hydrobromide
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.000005
5-chloro-6-fluoro-3-hydroxyquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.000008
5-ethyl-3-hydroxyquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.000008
5-fluoro-3-hydroxyquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.0005
5-hydroxy-2-(2-phenylethyl)-4H-pyran-4-one
Homo sapiens
pH and temperature not specified in the publication
0.05
5-hydroxy-2-(methoxymethyl)-4H-pyran-4-one
Homo sapiens
pH and temperature not specified in the publication
0.0009
5-hydroxy-2-(phenoxymethyl)-4H-pyran-4-one
Homo sapiens
pH and temperature not specified in the publication
0.0009
5-hydroxy-2-[(naphthalen-1-yloxy)methyl]-4H-pyran-4-one
Homo sapiens
pH and temperature not specified in the publication
0.0008
5-hydroxy-2-[(naphthalen-2-yloxy)methyl]-4H-pyran-4-one
Homo sapiens
pH and temperature not specified in the publication
0.0002
5-hydroxy-2-[(phenylsulfanyl)methyl]-4H-pyran-4-one
Homo sapiens
pH and temperature not specified in the publication
0.003
5-hydroxy-2-[(pyridin-3-yloxy)methyl]-4H-pyran-4-one
Homo sapiens
pH and temperature not specified in the publication
0.004
5-hydroxy-2-[(pyrimidin-2-ylsulfanyl)methyl]-4H-pyran-4-one
Homo sapiens
pH and temperature not specified in the publication
0.000155
6-chloro-3-hydroxyquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.000009
6-fluoro-3-hydroxyquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.000069
6-[2-[4-(3-chlorophenyl)-7-hydroxy-2-oxo-2H-1-benzopyran-6-yl]ethyl]-4-hydroxypyridazin-3(2H)-one
Homo sapiens
pH 8, 37°C
-
0.000119
6-[2-[4-(4-chlorophenyl)-7-hydroxy-2-oxo-2H-1-benzopyran-6-yl]ethyl]-4-hydroxypyridazin-3(2H)-one
Homo sapiens
pH 8, 37°C
-
0.0001
7-chloro-3-hydroxyquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.0226
7-ethyl-3-hydroxyquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.00001
7-fluoro-3-hydroxyquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.05
7-hydroxypyrido[2,3-b]pyrazin-6(5H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.000033
8-chloro-3-hydroxyquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.0144
8-ethyl-3-hydroxyquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.000003
8-fluoro-3-hydroxyquinolin-2(1H)-one
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.00049
[[4-[(4,5-dibromo-1H-pyrrole-2-carbonyl)amino]-1H-pyrrole-2-carbonyl](methyl)amino]acetic acid
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.04
2-(3,3-dimethylbutyl)-6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione
Homo sapiens
-
at pH 8.5 and 25°C
0.00044
2-[2-(1H-benzimidazol-1-yl)ethyl]-6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione
Homo sapiens
-
at pH 8.5 and 25°C
0.0001
3-(benzylsulfanyl)-5-hydroxy-1,2,4-triazin-6(1H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00007
3-benzyl-5-hydroxy-1,2,4-triazin-6(1H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0000039
3-hydroxy-5-(2-phenylethyl)pyridin-2(1H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.00014
3-hydroxy-5-methylpyridin-2(1H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.0015
3-hydroxypyridin-2(1H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.0000069
3-hydroxyquinolin-2(1H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.000004
3-hydroxyquinolin-2-(1H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0006
3-[(cyclohexylmethyl)sulfanyl]-5-hydroxy-1,2,4-triazin-6(1H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0002
3-[[(1,2-benzoxazol-3-yl)methyl]sulfanyl]-5-hydroxy-1,2,4-triazin-6(1H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00006
3-[[(2H-1,3-benzodioxol-5-yl)methyl]sulfanyl]-5-hydroxy-1,2,4-triazin-6(1H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00005
3-[[(3,4-dichlorophenyl)methyl]sulfanyl]-5-hydroxy-1,2,4-triazin-6(1H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00003
3-[[(4-chlorophenyl)methyl]sulfanyl]-5-hydroxy-1,2,4-triazin-6(1H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0003
3-[[(4-tert-butylphenyl)methyl]sulfanyl]-5-hydroxy-1,2,4-triazin-6(1H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00003
3-[[(6-fluoronaphthalen-2-yl)methyl]sulfanyl]-5-hydroxy-1,2,4-triazin-6(1H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0007
3-[[([1,1'-biphenyl]-3-yl)methyl]sulfanyl]-5-hydroxy-1,2,4-triazin-6(1H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00009
3-[[([1,1'-biphenyl]-4-yl)methyl]sulfanyl]-5-hydroxy-1,2,4-triazin-6(1H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0000049
4-hydroxy-6-(1-phenylethyl)pyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.0000038
4-hydroxy-6-(2-phenylethyl)pyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.000013
4-hydroxy-6-(3-phenylpropyl)pyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.0000022
4-hydroxy-6-(phenoxymethyl)pyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.0000021
4-hydroxy-6-[2-(3-methoxyphenyl)ethyl]pyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.0000029
4-hydroxy-6-[2-(4-methoxyphenyl)ethyl]pyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.0000084
4-hydroxy-6-[2-[2-(trifluoromethyl)phenyl]ethyl]pyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.0000024
4-hydroxy-6-[2-[3-(trifluoromethyl)phenyl]ethyl]pyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.000012
4-hydroxy-6-[2-[4-(trifluoromethyl)phenyl]ethyl]pyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.000047
5-chloro-3-hydroxypyridin-2(1H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.00006
5-hydroxy-3-(2-phenylethyl)-1,2,4-triazin-6(1H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.004
5-hydroxy-3-(3-phenylpropyl)-1,2,4-triazin-6(1H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.04
5-hydroxy-3-[(2-phenylethyl)sulfanyl]-1,2,4-triazin-6(1H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00005
5-hydroxy-3-[[(4-iodophenyl)methyl]sulfanyl]-1,2,4-triazin-6(1H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0000047
6-(2-cyclohexylethyl)-4-hydroxypyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.00067
6-(3,3-dimethylbutyl)-4-hydroxypyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.0003
6-cyclohexyl-4-hydroxypyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.0001
6-hydroxy-2-(2-(naphthalen-1-yl)ethyl)-1,2,4-triazine-3,5-(2H,4H)-dione
Homo sapiens
-
at pH 8.5 and 25°C
0.00007
6-hydroxy-2-(2-phenylethyl)-1,2,4-triazine-3,5(2H,4H)-dione
Homo sapiens
-
at pH 8.5 and 25°C
0.00026
6-hydroxy-2-(3-methylbutyl)-1,2,4-triazine-3,5(2H,4H)-dione
Homo sapiens
-
at pH 8.5 and 25°C
0.0017
6-hydroxy-2-(3-phenylpropyl)-1,2,4-triazine-3,5(2H,4H)-dione
Homo sapiens
-
at pH 8.5 and 25°C
0.00005
6-hydroxy-2-[(naphthalen-1-yl)methyl]-1,2,4-triazine-3,5(2H,4H)-dione
Homo sapiens
-
at pH 8.5 and 25°C
0.00022
6-hydroxy-2-[(naphthalen-2-yl)methyl]-1,2,4-triazine-3,5(2H,4H)-dione
Homo sapiens
-
at pH 8.5 and 25°C
0.00033
6-hydroxy-2-[2-(1H-pyrazol-1-yl)ethyl]-1,2,4-triazine-3,5(2H,4H)-dione
Homo sapiens
-
at pH 8.5 and 25°C
0.00031
6-hydroxy-2-[2-(1H-pyrrolo[2,3-b]pyridin-1-yl)ethyl]-1,2,4-triazine-3,5(2H,4H)-dione
Homo sapiens
-
at pH 8.5 and 25°C
0.00076
6-hydroxy-2-[2-(pyridin-2-yl)ethyl]-1,2,4-triazine-3,5(2H,4H)-dione
Homo sapiens
-
at pH 8.5 and 25°C
0.00012
6-[(E)-2-(4-chlorophenyl)vinyl]-4-hydroxypyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.000002
6-[2-(2-fluorophenyl)ethyl]-4-hydroxypyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.0000015
6-[2-(3,5-difluorophenyl)ethyl]-4-hydroxypyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.000013
6-[2-(3,5-dimethoxyphenyl)ethyl]-4-hydroxypyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.0000014
6-[2-(3-fluorophenyl)ethyl]-4-hydroxypyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.0000027
6-[2-(4-chlorophenyl)ethyl]-4-hydroxypyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.0000031
6-[2-(4-fluorophenyl)ethyl]-4-hydroxypyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.000063
6-[2-[3,5-bis(trifluoromethyl)phenyl]ethyl]-4-hydroxypyridazin-3(2H)-one
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.00113
7-chloro-8-methyl-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione
Homo sapiens
-
at pH 8.2 and 37°C
0.00034
7-fluoro-8-methyl-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione
Homo sapiens
-
at pH 8.2 and 37°C
0.00138
8-bromo-7-chloro-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione
Homo sapiens
-
at pH 8.2 and 37°C
0.00021
8-chloro-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione
Homo sapiens
-
at pH 8.2 and 37°C
0.000008
3-hydroxy-1,8-naphthyridin-2(1H)-one hydrobromide
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.000009
3-hydroxy-1,8-naphthyridin-2(1H)-one hydrobromide
Homo sapiens
pH 8.5, recombinant enzyme, with substrate D-serine
0.0000014
4H-furo[3,2-b]pyrrole-5-carboxylic acid
Homo sapiens
-
in 50 mM potassium phosphate buffer (pH 7.5), at 22°C
0.00091
5-methylpyrazole-3-carboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.00019
6-chlorobenzo[d]isoxazol-3-ol
Homo sapiens
-
pH and temperature not specified in the publication
additional information
additional information
Homo sapiens
IC50 with substrate D-aspartate, overview
-
additional information
additional information
Homo sapiens
-
IC50 with substrate D-aspartate, overview
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.4 - 6.3
-
the apoprotein gives a single band whose pI of 6.3 is very close to the theoretical value of 6.36, the holoenzyme yields three bands at pI 6.3, 5.9, and 5.4
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
DAO mRNA levels are positively correlated with age <2 years in the cerebellum and amygdala
higher expression of DAO mRNA in the cerebellum, but lower expression of DAO protein in the cerebellum compared to the other brain regions studied. DAO mRNA levels are positively correlated with age <2 years in the cerebellum and amygdala
additional information
post-mortem brain. DAOA protein but not DAOA mRNA is detected in all brain regions studied, with a significant positive correlation (controlled for age) between DAO and DAO activator protein in all of the brain regions studied except for the frontal cortex
-
gene expression of DAAO in a post-mortem study of elderly patients with schizophrenia and non-affected controls in both hemispheres differentiating between gray and white matter, overview
-
in choroid plexus epithelial cells and glial cells of rhombencephalon. Higher level of DAO expression is observed in schizophrenic choroid plexus epithelial cells than that in non-schizophrenic cases
additional information
-
in situ hybridization and immunohistochemic determination
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
in human brain the flavoprotein D-amino acid oxidase is responsible for the degradation of the neuromodulator D-serine, an important effector of NMDA-receptor mediated neurotransmission
malfunction
physiological function
additional information
-
mutation R199W in the D-amino acid oxidase gene, DAO is associated with classical adult onset familial amyotrophic lateral sclerosis, FALS in a three generational FALS kindred, the 14.52 cMregiononchromosome 12q22-23 is linked to disease. Lentiviral-mediated expression of R199WDAO in primary motor neuron cultures causes increased TUNEL labeling. This effect also occurs in motor neurons cocultured on transduced astrocytes expressing R199W, indicating that the motor neuron cell death induced by this mutation is mediated by both cell autonomous and noncell autonomous processes
malfunction
-
an increase in DAO expression in parts of the brain is involved in aberrant D-amino acid metabolism
malfunction
-
the DAAO risk gene is associated with schizophrenia, linkage between DAAO and schizophrenia in a severely affected subpopulation of schizophrenia patients, genotyping, expression analysis, and detailed overview
malfunction
-
a total loss of enzymatic activity is associated with the adult onset of familial amyotrophic lateral sclerosis. Altered enzyme expression levels and activity have been reported in schizophrenia
physiological function
-
DAAO is involved in the degradation of the gliotransmitter D-serine, an important modulator of NMDA-receptor-mediated neurotransmission. An increase in DAAO activity, yielding a decrease in D-serine concentration, is among the molecular mechanisms leading to the onset of schizophrenia susceptibility, overview
physiological function
-
DAAO plays a key role in the pathophysiology of schizophrenia
physiological function
-
DAO may regulate D-amino acid concentration by modulating the cerebrospinal fluid
physiological function
-
physiological role of D-amino acids and DAAOs, regulation of the nervous system, hormone secretion, and other processes by D-amino acids, detailed overview
physiological function
-
the enzymatic function of DAAO is required for AHR activation by D-Trp and D-Tyr. DAAO catalyzes the production of aryl hydrocarbon receptor, AHR, agonists through the enzymatic conversion of D-tryptophan to indole-3-pyruvic acid, followed by nonenzymatic oxidation and condensation of indole-3-pyruvic acid is a critical step in the generation of receptor agonists by DAAO and aspartate aminotransferase, AST. Products of this process include the two agonists, 1,3-di(1H-indol-3-yl)propan-2-one and 1-(1H-indol-3-yl)-3-(3H-indol- 3-ylidene) propan-2-one, overview
physiological function
-
the enzyme is involved in glutamate receptor function, reported associations with negative symptoms and with anxiety and depression, respectively
physiological function
-
the enzyme is involved in the development of schizophrenia, mechanism, overview
physiological function
-
the enzyme modulates the function of the N-methyl D-aspartate receptor contributing to the involvement of the receptor signalling in schizophrenia
physiological function
-
the enzyme is part responsible for the significant increases in brain kynurenic acid levels seen under inflammatory conditions
physiological function
-
the enzyme is involved in schizophrenia and amyotrophic lateral sclerosis
physiological function
-
presence of DAO activator protein DAOA/G72 increases DAO activity only in HEK-293 cells, but has no effect on DAO activity in SH-SY5Y and 1321-N1 cells. The DAO holoenzyme becomes more flexible and misfolded in the presence of DAOA, whereas DAOA has no effect on DAO apoprotein. DAOA displays no effect on NMDA receptor activity in NR1/NR2A HEK-293 cells
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). OXDA_HUMAN
347
0
39474
Swiss-Prot
Secretory Pathway (Reliability: 4)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
80000
40000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
additional information
-
hDAAO exists as an equilibrium of holo- and apoprotein forms in solution
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme with bound inhibitor 3-hydroxyquinolin-2(1H)-one, X-ray diffraction structure determination and analysis
fluorescence lifetimes are 47 ps in the dimer, 235 ps in the monomer. The fluorescence lifetimes of the hDAAO did not change upon the inhibitor bindings. Three fastest electron transfer donors are Tyr314, Trp52 and Tyr224 in the dimer, while Tyr314, Tyr224 and Tyr55 in the monomer
molecular modeling of active site loop of wild-type and amyotrophic lateral sclerosis?associated DAO mutants such as R199W, R38H, R199Q, and Q201R
search for binding pockets of DAO to its inhibitor 4-bromo-3-nitrobenzoate by combining in silico docking simulation and labeling experiments employing an N-sulfanylethylanilide-based labeling technology. There are two binding pockets: one is shared with D-Ser and FAD, and the other is an cleft between the subunits of a DAO dimer
structure of mutant P219L in complex with FAD and benzoate at 2.25 A resolution displays conformational changes of the active site and lid. The distances between the H-bond-forming atoms of arginine 283 and benzoate and the relative position between the aromatic rings of tyrosine 224 and benzoate are changed in the P219L complex
structures of DAO in complex with thiophene carboxylic acid inhibitors. Residue Tyr224 is tightly stacked with the thiophene ring of the inhibitors, resulting in the disappearance of the secondary pocket observed with other DAO inhibitors. Tyr224 prefers the stacked conformation irrespective of whether Tyr224 is stacked or not in the initial state of the simulations. The active site is tightly closed with an extensive network of hydrogen bonds including those from Tyr224 in the stacked conformation
substrate-free or in complex with imino-DOPA, hanging drop vapour diffusion method, at 20°C
hanging-drop vapor diffusion method, crystal structure of the enzyme in complex with the competitive inhibitor benzoate at a resolution of 2.5 A
-
in complex with D-serine or 3,4-dihydroxy-D-phenylalanine, hanging drop vapour diffusion method
-
sitting drop vapor diffusion method, using 10-15% (w/v) PEG 4000, 0.1 M sodium citrate, pH 8.0, 0.2 M ammonium dihydrogen phosphate, and 10% (v/v) glycerol
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
G183R
inactive apoprotein, substitution negatively affects the ability to bind the flavin cofactor in the correct orientation. The overexpressed G183R protein is not fully targeted to peroxisomes, shows colocalization with ubiquitin, and increases 7fold both the D-serine cellular concentration and the D/(D+L)-serine ratio
L56T
increase in activity towards D-alanine, decrease in activity towards D-serine, D-tryptophan
P219L
mutation to corresponding residue of porcine DAO. The turnover numbers (kcat) of P219L are unchanged, but its Km values are decreased compared with wild-type, leading to an increase in the catalytic efficiency (kcat/Km). Benzoate inhibits P219L with lower Ki value
R120E
substitution in order to mimic the active nuclear translocation signal, slightly alters protein conformation, thermal stability, and kinetic properties, while the dimeric structure and the ligand-binding properties are unchanged. Mutant shows an increase in cytosolic localization that promotes nuclear targeting, without affecting cell viability
R120L
substitution in order to eliminate the positive charge, slightly alters protein conformation, thermal stability, and kinetic properties, while the dimeric structure and the ligand-binding properties are unchanged
R199W
transgenic mice overexpressing mutant R199W show marked abnormal motor features, e.g. kyphosis, associated with a significant loss (19%) of lumbar spinal cord motor neurons, analyzed at 14 months. This effect is greater in females. In transgenic mice expressing mutant R199W and superoxide dismutase SOD1 G93A mutant, overall survival is not affected, but the onset of neurological signs is significantly earlier in female double transgenic animals than their female SOD1 G93A littermates
Y55A
slight reduction in activity towards D-alanine, D-serine, increase in activity towards D-tryptophan, D-histidine, D-methionine, D-phenylalanine, D-tyrosine
Y55A/L56T
about 40-60% reduction in activity towards D-alanine, D-serine, slight reduction in activity towards D-tryptophan
Y55W
20-40% reduction in activity towards D-alanine, D-serine, no change in activity towards D-tryptophan
Y55W/L56T
50-70% reduction in activity towards D-alanine, D-serine, no change in activity towards D-tryptophan
R199W
-
naturally occuring mutation, the mutation in the D-amino acid oxidase gene is associated with classical adult onset familial amyotrophic lateral sclerosis the 14.52 cM region on chromosome 12q22-23 is linked to disease. Neuronal cell lines expressing R199W DAO show decreased viability and increased ubiquitinated aggregates compared with cells expressing the wild-type protein, overview. Lentiviral-mediated expression of mutant R199W DAO in primary motor neuron cultures causes increased TUNEL labeling
additional information
additional information
DAO variants including V5A, D46N, F90V, P103L, R115W, P119L, L215F, P268S, R283Q, R286C, L329F and G331E significantly reduce fluctuations around the active site loop residues and close to the hydrophobic stretch region of residues 47-51. In molecular dynamics simulations, V5A, D46N, F90V, P103L, R115W, P119L, L215F, P268S, R283Q, R286C, L329F and G331E variants exhibit nearly similar radius of gyration, the H78Y, R279Q and S340F variants including the wild-type exhibit a slightly increased profile. Variants V5A, D46N, F90V, P103L, R115W, P119L, L215F, P268S, R283Q, R286C, L329F and G331E experience more compact structure than wild-type and H78Y, R279Q and S340F during the course of simulations
additional information
-
DAO variants including V5A, D46N, F90V, P103L, R115W, P119L, L215F, P268S, R283Q, R286C, L329F and G331E significantly reduce fluctuations around the active site loop residues and close to the hydrophobic stretch region of residues 47-51. In molecular dynamics simulations, V5A, D46N, F90V, P103L, R115W, P119L, L215F, P268S, R283Q, R286C, L329F and G331E variants exhibit nearly similar radius of gyration, the H78Y, R279Q and S340F variants including the wild-type exhibit a slightly increased profile. Variants V5A, D46N, F90V, P103L, R115W, P119L, L215F, P268S, R283Q, R286C, L329F and G331E experience more compact structure than wild-type and H78Y, R279Q and S340F during the course of simulations
additional information
mutations in residues located on the loops on the border between the active site and the secondary binding pocket. Mutations modulate substrate specificity, product egress and enzyme activity
additional information
-
mutations in residues located on the loops on the border between the active site and the secondary binding pocket. Mutations modulate substrate specificity, product egress and enzyme activity
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
D-amino acid oxidase fused to an elastin-like polypeptide exhibits enzymatic activity that is about 1.6times that of the free enzyme and shows higher stability
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
use of surface layer (S-layer) protein of Lactobacillus brevis as a self-aggregating protein tag to enable cost-effective separation of human and yeast D-amino acid oxidases expressed in Escherichia coli cells. Human and yeast D-amino acid oxidases fused with S-layer proteins can be easily separated by aggregates at the interface and/or in a few conditions by precipitates to the bottom of the PEG-phosphate aqueous system
recombinant enzyme by ammonium sulfate fractionation, anion exchange chromatography, and dialysis
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
expression of EGFP-tagged DAAO in U-87 glioblastoma cells, transient coexpression of pLG72
expression of recombinant enzyme, using the CYP1A1 promoter, in murine hepatoma Hepa1c1c7 cells
-
functional enzyme overexpression in Escherichia coli strain BL21(DE3), method optimization and upscaling, detailed overview
-
genotyping of the enzyme in healthy and schizophrenic individuals, association between dysbindin and DAO single nucleotide polymorphisms and the positive and negative syndrome scale, PANSS, overview. Significant association between the dysbindin SNP rs3213207 and severity of both negative symptoms and total symptom load, as well as between the DAO SNP rs2070587 and total symptom score and severity of anxiety and depression
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
higher level of DAO expression is observed in schizophrenic choroid plexus epithelial cells than that in non-schizophrenic cases
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
holo- and apoprotein samples of hDAAO are incubated for 60 min at 15°C in a buffer containing different concentrations of urea, 0-6 M, and then refolded by 10fold dilution in 50 mM sodium diphosphate, pH 8.0, 5% glycerol and 15°C, in the presence of a 10fold molar excess of FAD. Chemical denaturation of hDAAO holoenzyme is partially reversible, 50% of the initial activity is recovered starting with the refolding from 4 M urea-denatured holoprotein, while the refolding of apoprotein is largely irreversible even at 2 M urea , 15-20% of recovery of enzymatic activity versus 90-100% for the holoenzyme and even in the presence of the cofactor
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
protocols for a variety of direct assays based on the determination of molecular oxygen consumption, reduction of alternative electron acceptors, or alpha-keto acid production, of coupled assays to detect the hydrogen peroxide or the ammonium production, and an indirect assay of the alpha-keto acid production based on a chemical derivatization
medicine
synthesis
use of surface layer (S-layer) protein of Lactobacillus brevis as a self-aggregating protein tag to enable cost-effective separation of human and yeast D-amino acid oxidases expressed in Escherichia coli cells. Human and yeast D-amino acid oxidases fused with S-layer proteins can be easily separated by aggregates at the interface and/or in a few conditions by precipitates to the bottom of the PEG-phosphate aqueous system
drug development
medicine
pharmacology
-
co-administration of the enzyme inhibitor 5-chloro-benzo[d]isoxazol-3-ol significantly enhances the efficacy of D-serine in attenuating prepulse inhibition deficits by administration of dizocilpine, an NMDA receptor antagonist. Therefore, co-administration of D-serine and a DAAO inhibitor has therapeutic potential for the treatment of schizophrenia
medicine
comprehensive analysis of catalogued DAAO rare variants triggering amyotrophic lateral sclerosis. Certain rare variants disrupt key interactions with the active site and decrease the conformational flexibility of active site loop comprising residues 216-228, which is essential for substrate binding and product release. These variants lost crucial interactions with the cofactor flavin-adenine-dinucleotide, resulting in weaker binding affinity
medicine
in blood serum of individuals with amnestic mild cognitive impairment, mild Alzheimer's disease, moderate to severe Alzheimer's disease, and healthy elderly, the DAO levels increase with the severity of the cognitive deficits. DAO levels are significantly associated with D-glutamate and D-serine levels
medicine
molecular dynamics simulations of wild-type, and all reported amyotrophic lateral sclerosis-associated DAO mutants. The mutations disrupt several key interactions with the active site residues and decrease the conformational flexibility of active site loop comprising 216 to 228 residues, necessary for substrate binding and product release, mainly due to the distortion of critical salt bridge and hydrogen bond interactions compared with wild-type. DAO mutants have a lower binding affinity toward cofactor flavin adenine dinucleotide and substrate iminoserine than the wildtype
medicine
transgenic mice overexpressing mutant R199W show marked abnormal motor features, e.g. kyphosis, associated with a significant loss (19%) of lumbar spinal cord motor neurons, analyzed at 14 months. This effect is greater in females. In transgenic mice expressing mutant R199W and superoxide dismutase SOD1 G93A mutant, overall survival is not affected, but the onset of neurological signs is significantly earlier in female double transgenic animals than their female SOD1 G93A littermates
drug development
-
the enzyme is a potential therapeutic target for schizophrenia treatment
medicine
-
D-serine availability in the nervous system may be altered in schizophrenia because of increased D-amino acid degradation by DAAO
medicine
-
involvement of DAO (and the interacting gene DAO activator) with a cluster of symptoms involving guilt, anxiety and depression in schizophrenia patients
medicine
-
the enzyme inhibition might have an therapeutic effect in schizophrenia treatment
medicine
-
the purified recombinant or native enzyme is used in therapeutic treatment of cancer combined with injection of D-proline. The enzyme is a target in the development of medical treatment for neurodegeneration and cancer
medicine
-
the enzyme is a potential valuable tool for cancer treatments that exploit the production of H2O2
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Raibekas, A.A.; Fukui, K.; Massey, V.
Design and properties of human D-amino acid oxidase with covalently attached flavin
Proc. Natl. Acad. Sci. USA
97
3089-3093
2000
Homo sapiens
Pilone, M.S.
D-Amino acid oxidase: new findings
Cell. Mol. Life Sci.
57
1732-1747
2000
Homo sapiens, Rhodotorula toruloides, Sus scrofa, Trigonopsis variabilis
Molla, G.; Sacchi, S.; Bernasconi, M.; Pilone, M.S.; Fukui, K.; Polegioni, L.
Characterization of human D-amino acid oxidase
FEBS Lett.
580
2358-2364
2006
Homo sapiens
Kawazoe, T.; Tsuge, H.; Pilone, M.S.; Fukui, K.
Crystal structure of human D-amino acid oxidase: context-dependent variability of the backbone conformation of the VAAGL hydrophobic stretch located at the si-face of the flavin ring
Protein Sci.
15
2708-2717
2006
Homo sapiens
Verrall, L.; Walker, M.; Rawlings, N.; Benzel, I.; Kew, J.N.; Harrison, P.J.; Burnet, P.W.
D-Amino acid oxidase and serine racemase in human brain: normal distribution and altered expression in schizophrenia
Eur. J. Neurosci.
26
1657-1669
2007
Homo sapiens
Corvin, A.; McGhee, K.A.; Murphy, K.; Donohoe, G.; Nangle, J.M.; Schwaiger, S.; Kenny, N.; Clarke, S.; Meagher, D.; Quinn, J.; Scully, P.; Baldwin, P.; Browne, D.; Walsh, C.; Waddington, J.L.; Morris, D.W.; Gill, M.
Evidence for association and epistasis at the DAOA/G30 and D-amino acid oxidase loci in an Irish schizophrenia sample
Am. J. Med. Genet. B Neuropsychiatr. Genet.
144B
949-953
2007
Homo sapiens
Halvey, P.J.; Hansen, J.M.; Johnson, J.M.; Go, Y.M.; Samali, A.; Jones, D.P.
Selective oxidative stress in cell nuclei by nuclear-targeted D-amino acid oxidase
Antioxid. Redox Signal.
9
807-816
2007
Homo sapiens
Kawazoe, T.; Tsuge, H.; Imagawa, T.; Aki, K.; Kuramitsu, S.; Fukui, K.
Structural basis of D-DOPA oxidation by D-amino acid oxidase: altersodiumtive pathway for dopamine biosynthesis
Biochem. Biophys. Res. Commun.
355
385-391
2007
Homo sapiens (P14920), Homo sapiens
Sparey, T.; Abeywickrema, P.; Almond, S.; Brandon, N.; Byrne, N.; Campbell, A.; Hutson, P.H.; Jacobson, M.; Jones, B.; Munshi, S.; Pascarella, D.; Pike, A.; Prasad, G.S.; Sachs, N.; Sakatis, M.; Sardana, V.; Venkatraman, S.; Young, M.B.
The discovery of fused pyrrole carboxylic acids as novel, potent D-amino acid oxidase (DAO) inhibitors
Bioorg. Med. Chem. Lett.
18
3386-3391
2008
Homo sapiens (P14920)
Pollegioni, L.; Piubelli, L.; Sacchi, S.; Pilone, M.S.; Molla, G.
Physiological functions of D-amino acid oxidases: from yeast to humans
Cell. Mol. Life Sci.
64
1373-1394
2007
Chlorella vulgaris, Rattus norvegicus (O35078), Sus scrofa (P00371), Homo sapiens (P14920), Homo sapiens, Mus musculus (P18894), Rhodotorula toruloides (P80324), Cyprinus carpio (Q6TGN2), Trigonopsis variabilis (Q99042), [Candida] boidinii (Q9HGY3)
Kawazoe, T.; Park, H.K.; Iwana, S.; Tsuge, H.; Fukui, K.
Human D-amino acid oxidase: an update and review
Chem. Rec.
7
305-315
2007
Homo sapiens
Pollegioni, L.; Sacchi, S.; Caldinelli, L.; Boselli, A.; Pilone, M.S.; Piubelli, L.; Molla, G.
Engineering the properties of D-amino acid oxidases by a rational and a directed evolution approach
Curr. Protein Pept. Sci.
8
600-618
2007
Sus scrofa (P00371), Sus scrofa, Homo sapiens (P14920), Homo sapiens, Rhodotorula toruloides (P80324), Trigonopsis variabilis (Q99042)
Adage, T.; Trillat, A.C.; Quattropani, A.; Perrin, D.; Cavarec, L.; Shaw, J.; Guerassimenko, O.; Giachetti, C.; Greco, B.; Chumakov, I.; Halazy, S.; Roach, A.; Zaratin, P.
In vitro and in vivo pharmacological profile of AS057278, a selective D-amino acid oxidase inhibitor with potential anti-psychotic properties
Eur. Neuropsychopharmacol.
18
200-214
2008
Rattus norvegicus, Homo sapiens (P14920), Homo sapiens
Sacchi, S.; Bernasconi, M.; Martineau, M.; Mothet, J.P.; Ruzzene, M.; Pilone, M.S.; Pollegioni, L.; Molla, G.
pLG72 modulates intracellular D-serine levels through its interaction with D-amino acid oxidase: Effect on schizophrenia susceptibility
J. Biol. Chem.
283
22244-22256
2008
Homo sapiens, Sus scrofa
Iwana, S.; Kawazoe, T.; Park, H.K.; Tsuchiya, K.; Ono, K.; Yorita, K.; Sakai, T.; Kusumi, T.; Fukui, K.
Chlorpromazine oligomer is a potentially active substance that inhibits human D-amino acid oxidase, product of a susceptibility gene for schizophrenia
J. Enzyme Inhib. Med. Chem.
23
901-911
2008
Homo sapiens
Corvin, A.; Donohoe, G.; McGhee, K.; Murphy, K.; Kenny, N.; Schwaiger, S.; Nangle, J.M.; Morris, D.; Gill, M.
D-amino acid oxidase (DAO) genotype and mood symptomatology in schizophrenia
Neurosci. Lett.
426
97-100
2007
Homo sapiens
Madeira, C.; Freitas, M.E.; Vargas-Lopes, C.; Wolosker, H.; Panizzutti, R.
Increased brain D-amino acid oxidase (DAAO) activity in schizophrenia
Schizophr. Res.
101
76-83
2008
Homo sapiens
Williams, M.
Commentary: genome-based CNS drug discovery: D-amino acid oxidase (DAAO) as a novel target for antipsychotic medications: progress and challenges
Biochem. Pharmacol.
78
1360-1365
2009
Homo sapiens, Rattus norvegicus
Khoronenkova, S.V.; Tishkov, V.I.
D-amino acid oxidase: physiological role and applications
Biochemistry (Moscow)
73
1511-1518
2008
Homo sapiens, Sus scrofa, Rhodotorula toruloides (P80324), Trigonopsis variabilis (Q99042)
Hashimoto, K.; Fujita, Y.; Horio, M.; Kunitachi, S.; Iyo, M.; Ferraris, D.; Tsukamoto, T.
Co-administration of a D-amino acid oxidase inhibitor potentiates the efficacy of D-serine in attenuating prepulse inhibition deficits after administration of dizocilpine
Biol. Psychiatry
65
1103-1106
2009
Homo sapiens, Mus musculus
Nguyen, L.P.; Hsu, E.L.; Chowdhury, G.; Dostalek, M.; Guengerich, F.P.; Bradfield, C.A.
D-amino acid oxidase generates agonists of the aryl hydrocarbon receptor from D-tryptophan
Chem. Res. Toxicol.
22
1897-1904
2009
Homo sapiens, Sus scrofa (P00371)
Duplantier, A.J.; Becker, S.L.; Bohanon, M.J.; Borzilleri, K.A.; Chrunyk, B.A.; Downs, J.T.; Hu, L.Y.; El-Kattan, A.; James, L.C.; Liu, S.; Lu, J.; Maklad, N.; Mansour, M.N.; Mente, S.; Piotrowski, M.A.; Sakya, S.M.; Sheehan, S.; Steyn, S.J.; Strick, C.A.; Williams, V.A.; Zhang, L.
Discovery, SAR, and pharmacokinetics of a novel 3-hydroxyquinolin-2(1H)-one series of potent D-amino acid oxidase (DAAO) inhibitors
J. Med. Chem.
52
3576-3585
2009
Rattus norvegicus, Homo sapiens (P14920), Homo sapiens
Ono, K.; Shishido, Y.; Park, H.K.; Kawazoe, T.; Iwana, S.; Chung, S.P.; Abou El-Magd, R.M.; Yorita, K.; Okano, M.; Watanabe, T.; Sano, N.; Bando, Y.; Arima, K.; Sakai, T.; Fukui, K.
Potential pathophysiological role of D-amino acid oxidase in schizophrenia: immunohistochemical and in situ hybridization study of the expression in human and rat brain
J. Neural Transm.
116
1335-1347
2009
Homo sapiens, Rattus norvegicus (O35078)
Habl, G.; Zink, M.; Petroianu, G.; Bauer, M.; Schneider-Axmann, T.; von Wilmsdorff, M.; Falkai, P.; Henn, F.A.; Schmitt, A.
Increased D-amino acid oxidase expression in the bilateral hippocampal CA4 of schizophrenic patients: a post-mortem study
J. Neural Transm.
116
1657-1665
2009
Homo sapiens
Smith, S.M.; Uslaner, J.M.; Yao, L.; Mullins, C.M.; Surles, N.O.; Huszar, S.L.; McNaughton, C.H.; Pascarella, D.M.; Kandebo, M.; Hinchliffe, R.M.; Sparey, T.; Brandon, N.J.; Jones, B.; Venkatraman, S.; Young, M.B.; Sachs, N.; Jacobson, M.A.; Hutson, P.H.
The behavioral and neurochemical effects of a novel D-amino acid oxidase inhibitor compound 8 [4H-thieno [3,2-b]pyrrole-5-carboxylic acid] and D-serine
J. Pharmacol. Exp. Ther.
328
921-930
2009
Homo sapiens, Rattus norvegicus
Abou El-Magd, R.; Park, H.; Kawazoe, T.; Iwana, S.; Ono, K.; Chung, S.; Miyano, M.; Yorita, K.; Sakai, T.; Fukui, K.
The effect of risperidone on D-amino acid oxidase activity as a hypothesis for a novel mechanism of action in the treatment of schizophrenia
J. Psychopharmacol. (Oxford)
2009
1-13
2009
Homo sapiens, Mus musculus, Sus scrofa
Verrall, L.; Burnet, P.W.; Betts, J.F.; Harrison, P.J.
The neurobiology of D-amino acid oxidase and its involvement in schizophrenia
Mol. Psychiatry
15
122-137
2009
Homo sapiens
Wirgenes, K.V.; Djurovic, S.; Agartz, I.; Jonsson, E.G.; Werge, T.; Melle, I.; Andreassen, O.A.
Dysbindin and D-amino-acid-oxidase gene polymorphisms associated with positive and negative symptoms in schizophrenia
Neuropsychobiology
60
31-36
2009
Homo sapiens
Romano, D.; Molla, G.; Pollegioni, L.; Marinelli, F.
Optimization of human D-amino acid oxidase expression in Escherichia coli
Protein Expr. Purif.
68
72-78
2009
Homo sapiens
Caldinelli, L.; Molla, G.; Sacchi, S.; Pilone, M.S.; Pollegioni, L.
Relevance of weak flavin binding in human D-amino acid oxidase
Protein Sci.
18
801-810
2009
Homo sapiens
Mitchell, J.; Paul, P.; Chen, H.J.; Morris, A.; Payling, M.; Falchi, M.; Habgood, J.; Panoutsou, S.; Winkler, S.; Tisato, V.; Hajitou, A.; Smith, B.; Vance, C.; Shaw, C.; Mazarakis, N.D.; de Belleroche, J.
Familial amyotrophic lateral sclerosis is associated with a mutation in D-amino acid oxidase
Proc. Natl. Acad. Sci. USA
107
7556-7561
2010
Homo sapiens
Caldinelli, L.; Molla, G.; Bracci, L.; Lelli, B.; Pileri, S.; Cappelletti, P.; Sacchi, S.; Pollegioni, L.
Effect of ligand binding on human D-amino acid oxidase: implications for the development of new drugs for schizophrenia treatment
Protein Sci.
19
1500-1512
2010
Homo sapiens (P14920), Homo sapiens
Sacchi, S.; Caldinelli, L.; Cappelletti, P.; Pollegioni, L.; Molla, G.
Structure-function relationships in human D-amino acid oxidase
Amino Acids
43
1833-1850
2012
Homo sapiens
Raje, M.; Hin, N.; Duvall, B.; Ferraris, D.V.; Berry, J.F.; Thomas, A.G.; Alt, J.; Rojas, C.; Slusher, B.S.; Tsukamoto, T.
Synthesis of kojic acid derivatives as secondary binding site probes of D-amino acid oxidase
Bioorg. Med. Chem. Lett.
23
3910-3913
2013
Homo sapiens (P14920)
Hondo, T.; Warizaya, M.; Niimi, T.; Namatame, I.; Yamaguchi, T.; Nakanishi, K.; Hamajima, T.; Harada, K.; Sakashita, H.; Matsumoto, Y.; Orita, M.; Takeuchi, M.
4-Hydroxypyridazin-3(2H)-one derivatives as novel D-amino acid oxidase inhibitors
J. Med. Chem.
56
3582-3592
2013
Homo sapiens
Pollegioni, L.; Molla, G.
New biotech applications from evolved D-amino acid oxidases
Trends Biotechnol.
29
276-283
2011
Glutamicibacter protophormiae, [Candida] boidinii, Homo sapiens, Rhodotorula toruloides, Trigonopsis variabilis
Sacchi, S.
D-Serine metabolism new insights into the modulation of D-amino acid oxidase activity
Biochem. Soc. Trans.
41
1551-1556
2013
Homo sapiens
Hin, N.; Duvall, B.; Berry, J.F.; Ferraris, D.V.; Rais, R.; Alt, J.; Rojas, C.; Slusher, B.S.; Tsukamoto, T.
D-Amino acid oxidase inhibitors based on the 5-hydroxy-1,2,4-triazin-6(1H)-one scaffold
Bioorg. Med. Chem. Lett.
26
2088-2091
2016
Homo sapiens
Xie, D.; Lu, J.; Xie, J.; Cui, J.; Li, T.F.; Wang, Y.C.; Chen, Y.; Gong, N.; Li, X.Y.; Fu, L.; Wang, Y.X.
Discovery and analgesic evaluation of 8-chloro-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione as a novel potent D-amino acid oxidase inhibitor
Eur. J. Med. Chem.
117
19-32
2016
Homo sapiens, Rattus norvegicus, Sus scrofa
Sasabe, J.; Suzuki, M.; Imanishi, N.; Aiso, S.
Activity of D-amino acid oxidase is widespread in the human central nervous system
Front. Synaptic Neurosci.
6
14
2014
Homo sapiens
Chang, S.L.; Hsieh, C.H.; Chen, Y.J.; Wang, C.M.; Shih, C.S.; Huang, P.W.; Mir, A.; Lane, H.Y.; Tsai, G.E.; Chang, H.T.
The C-terminal region of G72 increases D-amino acid oxidase activity
Int. J. Mol. Sci.
15
29-43
2013
Homo sapiens
Du, K.; Sun, J.; Song, X.; Song, C.; Feng, W.
Enhancement of the solubility and stability of D-amino acid oxidase by fusion to an elastin like polypeptide
J. Biotechnol.
212
50-55
2015
Homo sapiens
Hopkins, S.C.; Heffernan, M.L.; Saraswat, L.D.; Bowen, C.A.; Melnick, L.; Hardy, L.W.; Orsini, M.A.; Allen, M.S.; Koch, P.; Spear, K.L.; Foglesong, R.J.; Soukri, M.; Chytil, M.; Fang, Q.K.; Jones, S.W.; Varney, M.A.; Panatier, A.; Oliet, S.H.; Pollegioni, L.; Piubelli, L.; Molla, G.; Nardini, M.; Large, T.H.
Structural, kinetic, and pharmacodynamic mechanisms of D-amino acid oxidase inhibition by small molecules
J. Med. Chem.
56
3710-3724
2013
Homo sapiens (P14920), Homo sapiens
Hin, N.; Duvall, B.; Ferraris, D.; Alt, J.; Thomas, A.G.; Rais, R.; Rojas, C.; Wu, Y.; Wozniak, K.M.; Slusher, B.S.; Tsukamoto, T.
6-Hydroxy-1,2,4-triazine-3,5(2H,4H)-dione derivatives as novel D-amino acid oxidase inhibitors
J. Med. Chem.
58
7258-7272
2015
Homo sapiens
Murtas, G.; Caldinelli, L.; Cappelletti, P.; Sacchi, S.; Pollegioni, L.
Human D-amino acid oxidase The inactive G183R variant
Biochim. Biophys. Acta
1866
822-830
2018
Homo sapiens (P14920), Homo sapiens
Szilagyi, B.; Skok, Z.; Racz, A.; Frlan, R.; Ferenczy, G.G.; Ilas, J.; Keseru, G.M.
Discovery of d-amino acid oxidase inhibitors based on virtual screening against the lid-open enzyme conformation
Bioorg. Med. Chem. Lett.
28
1693-1698
2018
Homo sapiens (P14920)
Ahn, M.; Park, S.; Jeon, J.; Choi, J.K.; Khang, Y.
Application of an S-layer protein as a self-aggregating tag for cost-effective separation of recombinant human and yeast D-amino acid oxidases in the aqueous two-phase system
Biotechnol. Lett.
42
241-248
2020
Homo sapiens (P14920), Rhodotorula toruloides (P80324), Rhodotorula toruloides ATCC 26217 (P80324)
Kato, Y.; Hin, N.; Maita, N.; Thomas, A.G.; Kurosawa, S.; Rojas, C.; Yorita, K.; Slusher, B.S.; Fukui, K.; Tsukamoto, T.
Structural basis for potent inhibition of D-amino acid oxidase by thiophene carboxylic acids
Eur. J. Med. Chem.
159
23-34
2018
Homo sapiens (P14920), Homo sapiens
Rosini, E.; Caldinelli, L.; Piubelli, L.
Assays of D-amino acid oxidase activity
Front. Mol. Biosci.
4
102
2017
Homo sapiens (P14920), Rhodotorula toruloides (P80324)
Murtas, G.; Sacchi, S.; Valentino, M.; Pollegioni, L.
Biochemical properties of human D-amino acid oxidase
Front. Mol. Biosci.
4
88
2017
Homo sapiens (P14920), Homo sapiens
Murtas, G.; Sacchi, S.; Pollegioni, L.
Substitution of arginine 120 in human D-amino acid oxidase favors FAD-binding and nuclear mistargeting
Front. Mol. Biosci.
6
125
2019
Homo sapiens (P14920), Homo sapiens
Jagannath, V.; Brotzakis, Z.; Parrinello, M.; Walitza, S.; Gruenblatt, E.
Controversial effects of D-amino acid oxidase activator (DAOA)/G72 on D-amino acid oxidase (DAO) activity in human neuronal, astrocyte and kidney cell lines The N-methyl D-aspartate (NMDA) receptor hypofunction point of view
Front. Mol. Neurosci.
10
342
2017
Homo sapiens
Jagannath, V.; Marinova, Z.; Monoranu, C.; Walitza, S.; Gruenblatt, E.
Expression of D-amino acid oxidase (DAO/DAAO) and D-amino acid oxidase activator (DAOA/G72) during development and aging in the human post-mortem brain
Front. Neuroanat.
11
31
2017
Homo sapiens (P14920), Homo sapiens
Rachadech, W.; Kato, Y.; Abou El-Magd, R.M.; Shishido, Y.; Kim, S.H.; Sogabe, H.; Maita, N.; Yorita, K.; Fukui, K.
P219L substitution in human D-amino acid oxidase impacts the ligand binding and catalytic efficiency
J. Biochem.
168
557-567
2020
Homo sapiens (P14920), Homo sapiens
Padhi, A.; Hazra, S.
Insights into the role of D-amino acid oxidase mutations in amyotrophic lateral sclerosis
J. Cell. Biochem.
120
2180-2197
2019
Homo sapiens (P14920), Homo sapiens
Taniguchi, S.; Chosrowjan, H.; Ito, S.; Miyasaka, H.; Katane, M.; Homma, H.; Tanaka, F.; Nueangaudom, A.; Lugsanangarm, K.; Kokpol, S.
Comparative studies on picosecond-resolved fluorescence of D-amino acid oxidases from human with one from porcine kidney. Photoinduced electron transfer from aromatic amino acids to the excited flavin
J. Photochem. Photobiol. B
198
111546
2019
Sus scrofa (P00371), Sus scrofa, Homo sapiens (P14920), Homo sapiens
Szilagyi, B.; Hargitai, C.; Kelemen, A.A.; Racz, A.; Ferenczy, G.G.; Volk, B.; Keseru, G.M.
Synthesis and biochemical evaluation of lid-open D-amino acid oxidase inhibitors
Molecules
24
290
2019
Homo sapiens (P14920)
Kohiki, T.; Kato, Y.; Nishikawa, Y.; Yorita, K.; Sagawa, I.; Denda, M.; Inokuma, T.; Shigenaga, A.; Fukui, K.; Otaka, A.
Elucidation of inhibitor-binding pockets of d-amino acid oxidase using docking simulation and N-sulfanylethylanilide-based labeling technology
Org. Biomol. Chem.
15
5289-5297
2017
Homo sapiens (P14920)
Kondori, N.; Paul, P.; Robbins, J.; Liu, K.; Hildyard, J.; Wells, D.; De Belleroche, J.
Characterisation of the pathogenic effects of the in vivo expression of an ALS-linked mutation in D-amino acid oxidase Phenotype and loss of spinal cord motor neurons
PLoS ONE
12
e0188912
2017
Homo sapiens (P14920)
Subramanian, K.; Gora, A.; Spruijt, R.; Mitusinska, K.; Suarez-Diez, M.; Martins Dos Santos, V.; Schaap, P.J.
Modulating D-amino acid oxidase (DAAO) substrate specificity through facilitated solvent access
PLoS ONE
13
e0198990
2018
Sus scrofa (P00371), Sus scrofa, Homo sapiens (P14920), Homo sapiens
Padhi, A.; Zhang, K.
Mechanistic insights into the loss-of-function mechanisms of rare human D-amino acid oxidase variants implicated in amyotrophic lateral sclerosis
Sci. Rep.
10
17146
2020
Homo sapiens (P14920), Homo sapiens
EXTERNAL LINKS (specific for EC-Number 1.4.3.3)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
