Information on EC 1.4.3.22 - diamine oxidase and Organism(s) Homo sapiens

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
1.4.3.22
-
RECOMMENDED NAME
GeneOntology No.
diamine oxidase
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
beta-alanine biosynthesis I
-
-
histamine degradation
-
-
N-methyl-Delta1-pyrrolinium cation biosynthesis
-
-
alanine metabolism
-
-
histidine metabolism
-
-
Arginine and proline metabolism
-
-
Histidine metabolism
-
-
Tryptophan metabolism
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
histamine:oxygen oxidoreductase (deaminating)
A group of enzymes that oxidize diamines, such as histamine, and also some primary monoamines but have little or no activity towards secondary and tertiary amines. They are copper quinoproteins (2,4,5-trihydroxyphenylalanine quinone) and, like EC 1.4.3.21 (primary-amine oxidase) but unlike EC 1.4.3.4 (monoamine oxidase), they are sensitive to inhibition by carbonyl-group reagents, such as semicarbazide.
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
hDAO is the frontline enzyme for histamine metabolism
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(8-arginine)-vasopressin + H2O + O2
?
show the reaction diagram
-
-
-
-
?
(8-lysine)-vasopressin + H2O + O2
?
show the reaction diagram
-
-
-
-
?
1,10-diaminodecane + H2O + O2
10-aminodecanal + NH3 + H2O2
show the reaction diagram
-
-
-
?
1,2-diaminoethane + H2O + O2
2-aminoethanal + NH3 + H2O2
show the reaction diagram
-
-
-
?
1,3-diaminopropane + H2O + O2
3-aminopropanal + NH3 + H2O2
show the reaction diagram
1,4-diaminobutane + H2O + O2
4-aminobutanal + NH3 + H2O2
show the reaction diagram
1,5-diaminopentane + H2O + O2
5-aminopentanal + NH3 + H2O2
show the reaction diagram
1,6-diaminohexane + H2O + O2
6-aminohexanal + NH3 + H2O2
show the reaction diagram
1,7-diaminoheptane + H2O + O2
7-aminoheptanal + NH3 + H2O2
show the reaction diagram
1,8-diaminooctane + H2O + O2
8-aminooctanal + NH3 + H2O2
show the reaction diagram
-
-
-
?
1,9-diaminononane + H2O + O2
9-aminononanal + NH3 + H2O2
show the reaction diagram
-
-
-
?
1-methylhistamine + H2O + O2
?
show the reaction diagram
-
-
-
-
?
2-methylhistamine + H2O + O2
?
show the reaction diagram
-
-
-
-
?
5-methylhistamine + H2O + O2
?
show the reaction diagram
-
-
-
-
?
agmatine
?
show the reaction diagram
-
14% of activity with putrescine
-
-
?
benzylamine + H2O + O2
benzaldehyde + NH3 + H2O2
show the reaction diagram
butylamine + H2O + O2
?
show the reaction diagram
-
-
-
-
?
cadaverine + H2O + O2
?
show the reaction diagram
-
-
-
-
?
collagen + H2O + O2
?
show the reaction diagram
-
-
-
-
?
ethylenediamine + H2O + O2
?
show the reaction diagram
-
-
-
-
?
histamine + H2O + O2
(imidazol-4-yl)acetaldehyde + NH3 + H2O2
show the reaction diagram
histamine + H2O + O2
?
show the reaction diagram
-
48% activity compared to putrescine
-
-
?
L-lysine methyl ester + H2O + O2
?
show the reaction diagram
-
-
-
-
?
methylhistamine + H2O + O2
?
show the reaction diagram
-
-
-
-
?
N(pi)-methylhistamine + H2O + O2
?
show the reaction diagram
-
-
-
-
?
N(tau)-methylhistamine + H2O + O2
?
show the reaction diagram
-
-
-
-
?
N-acetyl-1,4-diaminobutane + H2O + O2
N-acetyl-aminobutanal + acetylamine + H2O2
show the reaction diagram
-
8.6% of activity with putrescine
-
?
N-acetyl-1,5-diaminopentane + H2O + O2
N-acetyl-aminopentanal + acetylamine + H2O2
show the reaction diagram
-
3.8% of activity with putrescine
-
?
N1-acetyl-spermidine + H2O + O2
?
show the reaction diagram
-
8.6% of activity with putrescine
-
-
?
p-dimethylaminomethylbenzylamine + H2O + O2
?
show the reaction diagram
-
-
-
-
?
p-dimethylaminomethylbenzylamine + H2O + O2
p-dimethylaminomethylbenzaldehyde + NH3 + H2O2
show the reaction diagram
-
-
-
?
putrescine + H2O + O2
?
show the reaction diagram
putrescine + H2O + O2
gamma-aminobutyraldehyde + NH3 + H2O2
show the reaction diagram
-
-
-
-
?
RCH2NH2 + H2O + O2
RCHO + NH3 + H2O2
show the reaction diagram
spermidine + H2O + O2
?
show the reaction diagram
spermine + H2O + O2
?
show the reaction diagram
tropocollagen + H2O + O2
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
histamine + H2O + O2
(imidazol-4-yl)acetaldehyde + NH3 + H2O2
show the reaction diagram
RCH2NH2 + H2O + O2
RCHO + NH3 + H2O2
show the reaction diagram
-
enzyme plays a protective role against histamine in diseases such as ischaemic bowel syndrome, mesenteric infarction and ulcerative colitis
-
?
additional information
?
-
P19801
hDAO is unique among CAOs in that it has a distinct substrate preference for diamines
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,4,5-trihydroxyphenylalanine quinone
2,4,5-trihydroxyphenylalaninequinone
-
1.1 mol per mol of dimer
L-topaquinone
-
-
-
topaquinone
-
trihydroxyphenylalanine quinone
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
copper
Manganese
-
enzyme contains 1.2 gatom of manganese per 70000 Da subunit
Zn2+
the metal site is occupied approximately 25% by zinc
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(Z)-3-fluoro-2-(4-methoxybenzyl)allylamine hydrochloride
-
i.e. LJP 1586. Potent, specific, and orally available inhibitor of SSAO activity is an effective anti-inflammatory compound in vivo
4,4'-(pentane-1,5-diylbis(oxy))dibenzimidamide
noncompetitive inhibition
8-hydroxyquinoline
-
1 mM, 49.3% inhibition
aminoguanidine
azide
-
partially competitive with respect to oxidative half-reaction, competitive with respect to reductive half-reaction
Berenil
mixed inhibition
cimetidine
mixed inhibition
clonidine
mixed inhibition
Cuprizone
-
-
cyanide
-
1 mM, 76% inhibition
diethyldithiocarbamate
-
1 mM, complete inhibition
diminazene aceturate
-
-
Iproniazid
-
0.1 mM, 68% inhibition
Isoniazid
noncompetitive inhibition
NaCl
-
200 mM, approx. 50% inhibition, almost complete inhibition of the purified enzyme with 1 M NaCl
NaN3
-
-
Pentamidine
mixed inhibition
Quinacrine
-
1 mM, complete inhibition
Semicarbazide
Tranylcypromine
-
slight
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.13
1,3-Diaminopropane
-
pH 7.2, 37C
0.15
1,6-diaminohexane
-
pH 7.2, 37C
0.0034
1-Methylhistamine
-
pH 7.2, 37C
3.28
Acetylcadaverine
-
-
9.71
acetylputrescine
-
-
0.877 - 2.032
Butylamine
0.0279 - 0.03
cadaverine
0.63
ethylenediamine
-
pH 7.2, 37C
0.0028 - 0.124
histamine
2.8
L-Lysine methyl ester
-
pH 7.2, 37C
0.075 - 0.158
Methylhistamine
0.097
N(tau)-methylhistamine
-
-
0.625
N1-acetylspermidine
-
-
0.014
O2
-
30C, pH 7.2
0.11
p-dimethylaminomethylbenzylamine
-
pH 7.2, 37C
0.02 - 0.094
putrescine
0.033 - 9.52
spermidine
0.031 - 5.71
spermine
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
29220
1,3-Diaminopropane
-
pH 7.2, 37C
17580
1,6-diaminohexane
-
pH 7.2, 37C
6180
1-Methylhistamine
-
pH 7.2, 37C
27180
cadaverine
-
pH 7.2, 37C
7560
ethylenediamine
-
pH 7.2, 37C
8340
histamine
-
pH 7.2, 37C
20700
L-Lysine methyl ester
-
pH 7.2, 37C
4
O2
-
30C, pH 7.2, per dimer
32880
p-dimethylaminomethylbenzylamine
-
pH 7.2, 37C
5.5 - 28500
putrescine
11220
spermidine
-
pH 7.2, 37C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0011
4,4'-(pentane-1,5-diylbis(oxy))dibenzimidamide
-
37 - 92
azide
0.013
Berenil
-
0.09
cimetidine
-
0.1
clonidine
-
0.9
Isoniazid
-
0.29
Pentamidine
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.096
(Z)-3-fluoro-2-(4-methoxybenzyl)allylamine hydrochloride
Homo sapiens
-
-
0.000153
aminoguanidine
Homo sapiens
P19801
in 100 mM potassium phosphate buffer (pH 7.2), at 37C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.012
-
-
0.141
-
unpurified enzyme, at 37C, pH not specified in the publication
0.22
-
enzyme from seminal plasma
0.73
-
-
32.7
-
after 233fold purification, at 37C, pH not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 6.5
-
histane
6.4 - 6.6
-
histamine
6.5
-
putrescine and cadaverine
6.6 - 7
-
putrescine
7.2
assay at
8
-
N1-acetylspermidine
8.5
-
acetylcadaverine
9.5
-
spermidine and spermine
10 - 11
-
acetylputrescine
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.2 - 7.8
-
pH 6.2 and pH 7.8: about 75% activity, putrescine
6.2 - 8.2
-
pH 6.2: about 75% of maximal activity, pH 8.2: about 60% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
ascending, descending and transverse
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
mainly in cytoplasm but to a considerable extent also in mitochondrial fraction
Manually annotated by BRENDA team
-
mainly in cytoplasm but to a considerable extent also in mitochondrial fraction
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
80000
-
gel filtration, variable PAGE, ultracentrifugation
90000
-
2 * 90000, SDS-PAGE
102000
-
2 * 102000, SDS-PAGE
105000
-
2 * 105000, SDS-PAGE
200000
-
gel filtration
235000
-
sedimentation equilibrium
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
monomer
-
1 * 70000-80000, SDS-PAGE
additional information
hDAO has the archetypal CAO fold with each subunit of hDAO being comprised of domains D2, residues 27-135, D3, residues 144-258, and D4, residues 310-751. The domains are linked by loop regions consisting of residues 136-143 between D2 and D3 and residues 259-309 linking D3 to D4, structure and modelling, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in complex with aminoguanidine, hanging drop vapor diffusion method, using 0.1M bis-Tris propane (pH 7.5), 20% (w/v) PEG3350, and 0.2 M sodium sulfate at 20C
purified recombinant wild-type hDAO, hanging drop vapour diffusion, 200 nl protein solution, containing 10 mg/ml protein in 100 mM HEPES, pH 7.2, and 150 mM KCl, and 200 nl crystallant solution, containing 0.1 M MES, pH 6.5, and 12% w/v PEG 20000, are equilibrated over 0.075 ml reservoir solution at room temperature, eight weeks, method optimization using manually dispensed hanging-drop crystallization experiments containing 0.002 ml each of protein and crystallant equilibrated over 0.5 ml reservoir solution, best diffracting crystals grow using 0.1 M MES pH 6.1 and 12% w/v PEG at room temperature over a period of two months, X-ray diffraction structure determination and analysis at 2.1 A resolution
the structure of the native enzyme is determined by X-ray crystallography to a resolution of 1.8 A. The homodimeric structure has the archetypal amine oxidase fold. Two active sites, one in each subunit, are characterized by the presence of a copper ion and a topaquinone residue formed. Substrate binding pocket and entry channel of hDAO are distinctly different from other amine oxidases in accord with the different substrate specificities. The structures of two inhibitor complexes of hDAO, berenil and pentamidine, are refined to resolutions of 2.1 and 2.2 A, respectively. They bind noncovalently in the active-site channel. The inhibitor binding suggests that an aspartic acid residue, conserved in all diamine oxidases but absent from other amine oxidases, is responsible for the diamine specificity by interacting with the second amino group of preferred diamine substrates
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
unstable in dilute solution or in frozen state
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 24 h, 90% loss of activity
-
500 mM ammonium sulfate, 500 mM potassium phosphate, pH 7.4, stable for at least 3 weeks
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
affinity chromatography on AH-Sepharose
-
affinity chromatography on cadaverine-Sepharose
-
heparin-Sepharose column chromatography, phenyl-Sepharose column chromatography, CIM-QA column chromatography, and Superdex 200 gel filtration
-
recombinant enzyme
-
recombinant secreted hDAO from Drosophila S2 cells
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloned and expressed in Drosophila S2 cells
expressed in CHO-K1 cells
-
expressed in Drosophila melanogaster Schneider-2 cells
gene AOC1, expression of hDAO as a secreted enzyme in Drosophila S2 cells
overexpressed as a secreted enzyme under the control of a metallothionein promoter in Drosophila S2 cell culture
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
-
clinical impact of a commercial radioimmunoassay for determination of DAO activity for the diagnosis of histamine intolerance is evaluated in a prospective, multicentre study in 207 adult patients. No correlation between diamine oxidase serum levels and clinical status is be found
medicine
-
the balance between histamine and DAO seems to be crucial for an uncomplicated course of pregnancy. Reduced DAO activities are found in multiple heterogeneous complications of pregnancy such as diabetes, threatened and missed abortion and trophoblastic disorders. Low activities of the histamine-degrading enzyme DAO might indicate high-risk pregnancies, although high intra- and interindividual variations limit its value as a screening tool