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Information on EC 1.5.3.13 - N1-acetylpolyamine oxidase and Organism(s) Mus musculus and UniProt Accession Q8C0L6
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1.5.3.13 N1-acetylpolyamine oxidaseIUBMB Comments
The enzyme also catalyses the reaction: N1,N12-diacetylspermine + O2 + H2O = N1-acetylspermidine + 3-acetamamidopropanal + H2O2 . No or very weak activity with spermine, or spermidine in absence of aldehydes. In presence of aldehydes the enzyme catalyses the reactions: 1. spermine + O2 + H2O = spermidine + 3-aminopropanal + H2O2, and with weak efficiency 2. spermidine + O2 + H2O = putrescine + 3-aminopropanal + H2O2 . A flavoprotein (FAD). This enzyme, encoded by the PAOX gene, is found in mammalian peroxisomes and oxidizes N1-acetylated polyamines at the exo (three-carbon) side of the secondary amine, forming 3-acetamamidopropanal. Since the products of the reactions are deacetylated polyamines, this process is known as polyamine back-conversion. Differs in specificity from 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)], EC 1.5.3.16 (spermine oxidase) and EC 1.5.3.17 (non-specific polyamine oxidase).
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Word Map
- 1.5.3.13
- spermine
- putrescine
-
diamine
- ornithine
- oxidases
-
n1-acetyltransferase
- s-adenosylmethionine
- n1-acetylspermine
-
fad-dependent
-
monoamine
- 3-aminopropanal
- 1,3-diaminopropane
- cadaverine
- apoplastic
- aminoaldehydes
- aminoguanidine
- acrolein
-
back-conversion
- alpha-difluoromethylornithine
- samdc
-
n1-acetylated
- thermospermine
- norspermidine
- n8-acetylspermidine
-
tetraamine
-
1.4.3.6
- analysis
- medicine
- pharmacology
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
polyamine oxidase, paoh1, n1-acetylpolyamine oxidase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
additional information
-
PAO is a member of the monoamine oxidase family of flavoproteins
SYSTEMATIC NAME
IUBMB Comments
N1-acetylpolyamine:oxygen oxidoreductase (3-acetamidopropanal-forming)
The enzyme also catalyses the reaction: N1,N12-diacetylspermine + O2 + H2O = N1-acetylspermidine + 3-acetamamidopropanal + H2O2 [1]. No or very weak activity with spermine, or spermidine in absence of aldehydes. In presence of aldehydes the enzyme catalyses the reactions: 1. spermine + O2 + H2O = spermidine + 3-aminopropanal + H2O2, and with weak efficiency 2. spermidine + O2 + H2O = putrescine + 3-aminopropanal + H2O2 [2]. A flavoprotein (FAD). This enzyme, encoded by the PAOX gene, is found in mammalian peroxisomes and oxidizes N1-acetylated polyamines at the exo (three-carbon) side of the secondary amine, forming 3-acetamamidopropanal. Since the products of the reactions are deacetylated polyamines, this process is known as polyamine back-conversion. Differs in specificity from 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)], EC 1.5.3.16 (spermine oxidase) and EC 1.5.3.17 (non-specific polyamine oxidase).
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
N1-(3-[[(thiophen-2-yl)methyl]amino]propyl)octane-1,8-diamine + O2 + H2O
octane-1,8-diamine + N1-[(thiophen-2-yl)methyl]propanal + H2O2
-
-
-
?
N1-acetylspermidine + O2 + H2O
putrescine + 3-acetamidopropanal + H2O2
oxidized at the carbon on the exo-side of the N4-nitrogen
-
-
?
N1-benzyldodecane-1,12-diamine + O2 + H2O
dodecane-1,12-diamine + N1-benzylpropanal + H2O2
-
-
-
?
N1-benzylspermine + O2 + H2O
spermidine + 3-(benzylamino)propanal + H2O2
-
-
-
?
N1-[(naphthalen-2-yl)methyl]spermine + O2 + H2O
spermidine + N1-[(naphthalen-2-yl)methyl]propanal + H2O2
-
-
-
?
N1-[(pyridin-2-yl)methyl]spermine + O2 + H2O
spermidine + N1-[(pyridin-2-yl)methyl]propanal + H2O2
-
-
-
?
N1-[(thiophen-2-yl)methyl]spermine + O2 + H2O
spermidine + N1-[(thiophen-2-yl)methyl]propanal + H2O2
-
-
-
?
N1-acetylspermidine + O2 + H2O
putrescine + 3-acetaminopropanal + H2O2
-
-
-
?
N1-acetylspermine + O2 + H2O
spermidine + 3-acetaminopropanal + H2O2
-
-
-
?
N1-acetylspermine + O2 + H2O
spermidine + 3-acetamidopropanal + H2O2
-
-
-
?
N1-acetylspermine + O2 + H2O
spermidine + 3-acetamidopropanal + H2O2
oxidized at the carbon on the exo-side of the N4-nitrogen
-
-
?
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
N1-acetylspermidine + O2 + H2O
putrescine + 3-acetaminopropanal + H2O2
-
-
-
?
N1-acetylspermine + O2 + H2O
spermidine + 3-acetaminopropanal + H2O2
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1,12-diaminododecane
1,12-diaminododecane derivatives could represent good candidates for the development of novel highly specific mPAO inhibitors
6,6'-[ethane-1,2-diyldi(piperidine-4,1-diyl)]bis[N-[(2-methoxyphenyl)methyl]hexan-1-amine]
17fold selectivity for spermine oxidase over polyamine oxidase
-
methoctramine
120fold selectivity for spermine oxidase over polyamine oxidase
-
N1,N1'-(pentane-1,5-diyl)bis[N6-[(2-methoxyphenyl)methyl]hexane-1,6-diamine]
9fold selectivity for spermine oxidase over polyamine oxidase
-
N1,N7-bis(6-[[(2-methoxyphenyl)methyl]amino]hexyl)heptane-1,7-diamine
40fold selectivity for spermine oxidase over polyamine oxidase
-
MDL72527
irreversible. In addition to the covalent adduct, a second MDL72527 molecule is bound in the active site. Binding of MDL72527 is accompanied by altered conformations in the APAO backbone
additional information
no inhibition at pH 7.5: 1,8-diaminooctane. Comparative study on murine PAO (mPAO) and SMO (mSMO) inhibition. The different behaviour displayed by 1,12-diaminododecane towards mPAO and mSMO reveals the occurrence of basic differences in the ligand binding mode of the two enzymes, the first enzyme interacting mainly with substrate secondary amino groups and the second one with substrate primary amino groups. The data provide the basis for the development of novel and selective inhibitors able to discriminate between mammalian SMO and PAO activities
-
additional information
-
no inhibition at pH 7.5: 1,8-diaminooctane. Comparative study on murine PAO (mPAO) and SMO (mSMO) inhibition. The different behaviour displayed by 1,12-diaminododecane towards mPAO and mSMO reveals the occurrence of basic differences in the ligand binding mode of the two enzymes, the first enzyme interacting mainly with substrate secondary amino groups and the second one with substrate primary amino groups. The data provide the basis for the development of novel and selective inhibitors able to discriminate between mammalian SMO and PAO activities
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.001
N1-(3-[[(thiophen-2-yl)methyl]amino]propyl)octane-1,8-diamine
pH 7.5, 37°C
-
additional information
additional information
-
steady-state kinetics and rapid-reaction kinetics
-
additional information
additional information
steady-state kinetics and rapid-reaction kinetics
-
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
0.00044
6,6'-[ethane-1,2-diyldi(piperidine-4,1-diyl)]bis[N-[(2-methoxyphenyl)methyl]hexan-1-amine]
pH 7.5, 37°C
-
0.00053
N1,N1'-(pentane-1,5-diyl)bis[N6-[(2-methoxyphenyl)methyl]hexane-1,6-diamine]
pH 7.5, 37°C
-
0.000047
N1,N7-bis(6-[[(2-methoxyphenyl)methyl]amino]hexyl)heptane-1,7-diamine
pH 7.5, 37°C
-
additional information
additional information
-
inhibition kinetics, pH-dependence, overview
-
additional information
additional information
inhibition kinetics, pH-dependence, overview
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5 - 10
the rate constant for the reaction of the reduced enzyme with oxygen is not affected by a pH between 7.5 and 10
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
effects of pH on the steady-state and reductive half-reaction. Kinetics for N1-acetylspermine, N1-acetylspermidine, and spermine kcat/K(amine)-pH profiles are bell-shaped
additional information
effects of pH on the steady-state and reductive half-reaction. Kinetics for N1-acetylspermine, N1-acetylspermidine, and spermine kcat/K(amine)-pH profiles are bell-shaped
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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). PAOX_MOUSE
504
0
55447
Swiss-Prot
Mitochondrion (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
structure of APAO in its oxidized holo form and in complex with substrate and irreversible inhibitor MDL7252
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K315M
mutation has no effect on the kcat/Kamine profile for spermine. The kred value with N1-acetylspermine is 1.8fold lower in the mutant protein, and the pKa in the k(red)-pH profile with N1-acetylspermine shifts to 7.8. K315 does not play a critical role in amine oxidation by PAO
N313A
dramatic reduction in catalytic efficiency with substrate N1-acetylspermine
N313D
dramatic reduction in catalytic efficiency with substrate N1-acetylspermine
N313L
dramatic reduction in catalytic efficiency with substrate N1-acetylspermine
N313T
dramatic reduction in catalytic efficiency with substrate N1-acetylspermine
Y430F
mutation results in a 6fold decrease in the kcat value and the kcat/Km value for oxygen due to a comparable decrease in the rate constant for flavin reduction
K315M
site-directed mutagenesis, the mutant shows altered kinetics compared to the wild-type enzyme
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Royo, M.; Fitzpatrick, P.F.
Mechanistic studies of mouse polyamine oxidase with N1,N12-bisethylspermine as a substrate
Biochemistry
44
7079-7084
2005
Mus musculus (Q8C0L6), Mus musculus
Bianchi, M.; Polticelli, F.; Ascenzi, P.; Botta, M.; Federico, R.; Mariottini, P.; Cona, A.
Inhibition of polyamine and spermine oxidases by polyamine analogues
FEBS J.
273
1115-1123
2006
Mus musculus (Q8C0L6), Mus musculus
Henderson Pozzi, M.; Gawandi, V.; Fitzpatrick, P.F.
pH dependence of a mammalian polyamine oxidase: insights into substrate specificity and the role of lysine 315
Biochemistry
48
1508-1516
2009
Mus musculus, Mus musculus (Q8C0L6)
Wu, T.; Yankovskaya, V.; McIntire, W.S.
Cloning, sequencing, and heterologous expression of the murine peroxisomal flavoprotein, N1-acetylated polyamine oxidase
J. Biol. Chem.
278
20514-20525
2003
Mus musculus (Q8C0L6), Mus musculus
Sjogren, T.; Wassvik, C.; Snijder, A.; Aagaard, A.; Kumanomidou, T.; Barlind, L.; Kaminski, T.; Kashima, A.; Yokota, T.; Fjellstrom, O.
The structure of murine N1-acetylspermine oxidase reveals molecular details of vertebrate polyamine catabolism
Biochemistry
56
458-467
2017
Mus musculus (Q8C0L6)
Di Paolo, M.L.; Cervelli, M.; Mariottini, P.; Leonetti, A.; Polticelli, F.; Rosini, M.; Milelli, A.; Basagni, F.; Venerando, R.; Agostinelli, E.; Minarini, A.
Exploring the activity of polyamine analogues on polyamine and spermine oxidase methoctramine, a potent and selective inhibitor of polyamine oxidase
J. Enzyme Inhib. Med. Chem.
34
740-752
2019
Mus musculus (Q8C0L6)
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