Information on EC 1.5.3.16 - spermine oxidase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.5.3.16
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RECOMMENDED NAME
GeneOntology No.
spermine oxidase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
spermine + O2 + H2O = spermidine + 3-aminopropanal + H2O2
show the reaction diagram
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
beta-alanine biosynthesis IV
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spermine and spermidine degradation I
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spermine and spermidine degradation III
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Arginine and proline metabolism
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beta-Alanine metabolism
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SYSTEMATIC NAME
IUBMB Comments
spermidine:oxygen oxidoreductase (spermidine-forming)
The enzyme from Arabidopsis thaliana (AtPAO1) oxidizes norspermine to norspermidine with high efficiency [3]. The mammalian enzyme, encoded by the SMOX gene, is a cytosolic enzyme that catalyses the oxidation of spermine at the exo (three-carbon) side of the tertiary amine. No activity with spermidine. Weak activity with N1-acetylspermine. A flavoprotein (FAD). Differs in specificity from EC 1.5.3.13 (N1-acetylpolyamine oxidase), EC 1.5.3.14 (polyamine oxidase (propane-1,3-diamine-forming)), EC 1.5.3.15 (N8-acetylspermidine oxidase (propane-1,3-diamine-forming) and EC 1.5.3.17 (non-specific polyamine oxidase).
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
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Manually annotated by BRENDA team
gene SMOX
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1,16-diamino-4,8,13-triazahexadecane + O2 + H2O
?
show the reaction diagram
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increased activity compared to spermine
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?
1,16-diamino-4,8,13-triazahexadecane pentahydrochloride + O2 + H2O
?
show the reaction diagram
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-
-
-
?
alpha-methylspermine + O2 + H2O
?
show the reaction diagram
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-
-
-
?
benzylamidine + O2 + H2O
?
show the reaction diagram
-
-
-
-
?
N,N'-bis-(3-benzylaminopropyl)butane-1,4-diamine + O2 + H2O
N-(3-aminopropyl)-N'-(3-benzylaminopropyl)butane-1,4-diamine + N1-(3-benzylaminopropyl)butane-1,4-diamine + H2O2 + ?
show the reaction diagram
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main products
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?
N,N'-bis-(3-ethylaminopropyl)butane-1,4-diamine + O2 + H2O
N1-(3-ethylaminopropyl)butane-1,4-diamine + H2O2 + ?
show the reaction diagram
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minor N4-endo cleavage pathways resulting in formation of EtDAP
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?
N-(3-aminopropyl)-N-(3-ethylaminopropyl)butane-1,4-diamine + O2 + H2O
spermine + H2O2 + ?
show the reaction diagram
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i.e. N,N'-bis-(3-aminopropyl)butane-1,4-diamine
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?
N-(3-benzylaminopropyl)-N'-(3-ethylaminopropyl)butane-1,4-diamine + O2 + H2O
N1-(3-ethylaminopropyl)butane-1,4-diamine + H2O2 + ?
show the reaction diagram
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-
-
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?
N1-acetylspermidine + O2 + H2O
putrescine + 3-acetamidopropanal + H2O2
show the reaction diagram
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-
-
-
?
N1-acetylspermidine + O2 + H2O
putrescine + ?
show the reaction diagram
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-
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?
N1-acetylspermine + O2 + H2O
?
show the reaction diagram
N1-acetylspermine + O2 + H2O
N1-acetylspermidine + 3-aminopropanal + H2O2
show the reaction diagram
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-
-
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?
N1-acetylspermine + O2 + H2O
spermidine + 3-acetamidopropanal + H2O2
show the reaction diagram
N1-acetylspermine + O2 + H2O
spermidine + acetaminopropanal
show the reaction diagram
N1-acetylspermine + O2 + H2O
spermidine + N-acetyl-3-aminopropanal + H2O2
show the reaction diagram
N1-ethyl-spermine + O2 + H2O
spermidine + N-ethyl-3-aminopropanal + H2O2
show the reaction diagram
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good substrate
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-
?
N1-monoethylspermine + O2 + H2O
spermidine + ?
show the reaction diagram
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98% of the activity with spermine
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?
N8-acetylspermidine + O2 + H2O
1,3-diaminopropane + ?
show the reaction diagram
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-
-
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?
norspermidine + O2 + H2O
?
show the reaction diagram
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-
-
-
?
norspermine + O2 + H2O
?
show the reaction diagram
norspermine + O2 + H2O
? + H2O2
show the reaction diagram
spermidine + O2 + H2O
putrescine + 3-aminopropanal + H2O2
show the reaction diagram
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-
-
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?
spermine + O2 + H2O
?
show the reaction diagram
spermine + O2 + H2O
spermidine + 3-aminopropanal + H2O2
show the reaction diagram
spermine + O2 + H2O
spermidine + aminopropanal + H2O2
show the reaction diagram
thermospermine + O2 + H2O
?
show the reaction diagram
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-
-
?
thermospermine + O2 + H2O
? + H2O2
show the reaction diagram
tryptamine + O2 + H2O
?
show the reaction diagram
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?
additional information
?
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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
norspermine + O2 + H2O
?
show the reaction diagram
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-
-
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?
spermine + O2 + H2O
spermidine + 3-aminopropanal + H2O2
show the reaction diagram
thermospermine + O2 + H2O
?
show the reaction diagram
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-
-
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?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
flavin
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flavoprotein
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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copper and iron are not cofactors
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,12-diaminododecane
1,8-diaminooctane
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bis(ethyl)norspermine
dithioerythritol
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up to 0.010 mM increase the enzyme activity, higher concentrations inhibited it
dithiothreitol
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up to 0.010 mM increase the enzyme activity, higher concentrations inhibited it
guazatine
Iproniazid
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0.01 mM, 87% inhibition
Isoniazid
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0.01 mM, 81% inhibition
MDL 27391
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MDL 27695
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MDL 72145
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inhibited in a time-dependent manner. Half-life under saturation conditions is 0.8 min. MDL 72145 might be a chemical lead compound for the design of new chemotherapeutic agents against nematode infections
MDL 72527
MDL-72527
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0.2 mM, 41% inhibition
MDL72527
N,N' -bis(2,3-butadienyl)-1,4-butanediamine
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i.e. MDL72527
N,N1-bis(2,3-butadienyl)-1,4-butanediamine
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i.e. MDL72527, competitive. If incubated for longer times, MDL72527 yields irreversible inhibition of the enzyme with a half-life of 15 min at 0.1 mM MDL72527
N-prenylagmatine
N1,N11-diethylnorspermine
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0.2 mM, 21% inhibition
N1,N12-diethylspermine
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0.2 mM, 15% inhibition
N1,N14-diethylhomospermine
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0.2 mM, 49% inhibition
N1,N4-bis(2,3-butadienyl)-1,4 butanediamine
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i.e. MDL72527
N1,N4-bis(2,3-butadienyl)-1,4-butanediamine
N1-(n-octanesulfonyl)spermine
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0.2 mM, 86% inhibition
N1-ethyl-N11-(cyclopropyl)-methyl-4,8-diazaundecane
NEM
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0.01 mM, 85% inhibition
SL-11144
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potent inhibitor of PAOh1/SMO, IC50 below 0.01 mM
SL-11150
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potent inhibitor of PAOh1/SMO, IC50 below 0.01 mM
SL-11158
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potent inhibitor of PAOh1/SMO, IC50 below 0.01 mM
spermidine
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
HIV-1 Tat
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Tat-induced SMO activation, involving the polyamine-sensitive subtype of the NMDA receptor, the activation is completely prevented by the NMDAR antagonist MK-801. Mechanism, overview
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N1,N11-diethylnorspermine
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polyamine analogue with clinical relevance as an experimental anticancer agent. Treatment of human C-28/I2 chondrocytes rapidly induces spermidine/spermine N1-acetyltransferase and spermine oxidase activities, and down-regulates ornithine decarboxylase. The treatment does not provoke cell death and caspase activation when given alone for 24 h, but causes a caspase-3 and -9 dependent apoptosis in chondrocytes further exposed to cycloheximide. The simultaneous addition of N1,N11-diethylnorspermine and cycloheximide rapidly increases caspase activity in C-28/I2 cells in the absence of spermidine/spermineN1-acetyltransferase and spermine oxidase induction or significant reduction of polyamine levels
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.034 - 0.067
alpha-methylspermine
1.6
benzylamidine
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pH 8.5, 37°C
0.066
N1-acetylspermidine
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pH 9.0, 20°C
0.00158 - 2
N1-acetylspermine
0.027
N8-Acetylspermidine
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pH 9.0, 20°C
5
norspermidine
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pH 8.5, 37°C
0.09 - 6.9
norspermine
0.66
spermidine
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pH 8.5, 37°C
0.0005 - 0.53
spermine
0.02 - 5.7
thermospermine
2.5
tryptamine
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pH 8.5, 37°C
additional information
additional information
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
684
N1-acetylspermidine
Saccharomyces cerevisiae
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pH 9.0, 20°C
0.014 - 47
N1-acetylspermine
22.4
N8-Acetylspermidine
Saccharomyces cerevisiae
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pH 9.0, 20°C
0.09 - 6.9
norspermine
0.0208 - 165
spermine
0.02 - 5.7
thermospermine
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
10400
N1-acetylspermidine
Saccharomyces cerevisiae
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pH 9.0, 20°C
1932
0.43 - 29800
N1-acetylspermine
1108
841
N8-Acetylspermidine
Saccharomyces cerevisiae
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pH 9.0, 20°C
2661
7.7
norspermine
Arabidopsis thaliana
Q8H191, Q9FNA2
pH 8.0, temperature not specified in the publication
4120
0.00000005 - 16500
spermine
197
285
thermospermine
Arabidopsis thaliana
Q8H191, Q9FNA2
pH 8.0, temperature not specified in the publication
4728
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0117 - 1
1,12-diaminododecane
0.293
1,8-diaminooctane
pH 8.0, substrate: spermine
0.147
agmatine
pH 8.0, substrate: spermine
0.38
bis(ethyl)norspermine
0.0004 - 0.0007
guazatine
0.02
MDL 27695
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pH 8.5, 37°C
0.0009
MDL 72145
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0.063 - 0.1373
MDL72527
0.004 - 0.046
N-prenylagmatine
0.063
N1,N4-bis(2,3-butadienyl)-1,4-butanediamine
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isozyme SMOalpha, pH 8.0, temperature not specified in the publication
0.085
N1-ethyl-N11-(cyclopropyl)-methyl-4,8-diazaundecane
0.546
spermidine
pH 8.0, substrate: spermine
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 8.5
; recombinant His-tagged isozyme AtPAO4 with substrate spermine
9
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assay at
9 - 9.5
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mutant K367M
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 8.5
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recombinant wild-type MmSMO enzymatic activity increases in the pH range, reaching a maximum at pH 8.5 and decreasing for higher pH values
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
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assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.8
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isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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the antiproliferative effects of analogue N1,N1-bis(ethyl)norspermine in MDA-MB-231 cells are mediated in part through the production of H2O2 by SMO(PAOh1) and by the export of acetylated polyamines formed by the activity of spermidine/spermine N1-acetyltransferase
Manually annotated by BRENDA team
splice variant mSMO
Manually annotated by BRENDA team
splice variant mSMO
Manually annotated by BRENDA team
poor activity, splice variant mSMO
Manually annotated by BRENDA team
splice variant mSMO
Manually annotated by BRENDA team
poor activity, splice variant mSMO
Manually annotated by BRENDA team
poor activity, splice variant mSMO
Manually annotated by BRENDA team
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mononuclear inflammatory cells
Manually annotated by BRENDA team
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tissues from patients diagnosed with prostate cancer and prostatic intraepithelial neoplasia exhibit, on average, locally increased spermine oxidase (SMO) expression in regions of prostatic disease and higher overall SMO expression in prostatic epithelial cells compared to healthy individuals
Manually annotated by BRENDA team
splice variant mSMO
Manually annotated by BRENDA team
poor activity, splice variant mSMO
Manually annotated by BRENDA team
splice variant mSMO
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
; AtPAO4 is the major isoform in root peroxisomes
Manually annotated by BRENDA team
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
molecular modeling of enzyme and enzyme-spermine complex. Spermine oxidase binds spermine in a similar conformation as that observed in the yeast polyamine oxidase FMS1-spermine complex, with a major role for residues H82 and K367 in substrate binding and catalysis. The enzyme–substrate complex shows an active site pocket with highly polar characteristics
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
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complete loss of activity after 60 min
37
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complete loss of activity after 30 min
42
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complete loss of activity after 20 min
56
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complete loss of activity after 10 min
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, stable for 2 days minimal loss of activity, complete loss of enzyme activity after 14 days
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
; recombinant His-tagged AtPAO4 from Escherichia coli strain BL21(DE3)
recombinant enzyme
recombinant enzyme, SMO5; recombinant enzyme, SMO/PAOh1
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recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
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recombinant protein
recombinant protein purified by affinity chromatography and extensive dialysis
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recombinantly expressed mSMO isoforms
recombinantly produced mSMOmuDELTA (with a deletion of the nuclear domain)
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
AtPAO1 cDNA is isolated and cloned in a vector for heterologous expression in Escherichia coli
AtPAO1, DNA and amino acid sequence determination and analysis, intron/exon organization, sequence comparisons, expression of His6-tagged enzyme in Escherichia coli, expression of GFP-tagged AtPAO3 in Arabidopsis thaliana plants using the Agrobacterium tumefaciens (strain C58C1)-mediated floral dip transformation method
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cDNA is transiently transfected into HEK-293 cells
expression in Escherichia coli
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expression in Escherichia coli as a His-tagged protein; expression of His-tagged AtPAO4 in Escherichia coli strain BL21(DE3), transient expression of isozyme AtPAO4 in Arabidopsis thaliana root cell peroxisomes as monomeric red fluorescent protein fusion protein
expression in Escherichia coli BL21 DE3
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expression in HEK-293 cells
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expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
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expression of mutant mSMOmuDELTA (with a deletion of the nuclear domain) in Escherichia coli
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FMS1 gene cloned in frame with a C-terminal 6x His tag and expressed as a recombinant protein in Escherichia coli
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gene AtPAO1, construction of AtPAO::GUS transgenic Arabidopsis thaliana plants
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gene hSMO, expression in Escherichia coli strain BL21(DE3)
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gene SMOX, phylogenetic analysis
isozymes SMOalpha and SMOmu, exon structures of murine SMO splice variants, overview
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mSMO splice variants, expression in Escherichia coli and in in murine neuroblastoma N18TG2 cells
SMO5 cDNA is subcloned into the pET15b bacterial expression vector, expression in Escherichia coli. NCI-H157 human non-small cell lung carcinoma cells are stably transfected, and individual clones selected that overexpress the enzyme; SMO/PAOh1 cDNA is subcloned into the pET15b bacterial expression vector, expression in Escherichia coli. NCI-H157 human non-small cell lung carcinoma cells are stably transfected, and individual clones selected that overexpress the enzyme
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subcloned and expressed in secreted and secreted-tagged forms into Escherichia coli BL21 DE3 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
ability of Tat to upregulate the activity of spermine oxidase, the polyamine catabolic enzyme that specifically oxidizes spermine, with the production of spermidine, H2O2, and 3-aminopropanal, through stimulation of the NMDA receptor, mechanism, overview
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both the expression level of SMO mRNA and SMO enzyme activity are significantly lower in breast cancer samples compared to nontumor samples
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increased expression of spermine oxidase in ulcerative colitis and in prostate cancer and prostate intraepithelial neoplasia tissues. SMO expression is upregulated in gastritis tissues from patients with Helicobacter pylori infection, it is upregulated in both macrophages and epithelial cells
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no induction of SMO activity by N-alkylated polyamine analogues
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SMO is a highly inducible enzyme by a variety of stressful stimuli, including several antitumor polyamine analogues. Tumor-necrosis factor-alpha can induce H2O2 production via SMO gene upregulation
SMO transcript accumulation and enzymatic activity increase during C2C12 cell differentiation and correlate with the decrease of spermine content
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H82E
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no catalytic activity; site-directed mutagenesis, inactive mutant
H82Q
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about 300fold decrease in catalytic efficiency; site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
K367M
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about 3fold decrease in catalytic efficiency; site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
T428Y
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no catalytic activity
T528Y
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site-directed mutagenesis, inactive mutant
additional information
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
protein is first purified from the cell lysate under denaturing conditions and renatured by dialysis against decreasing concentrations of urea
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine