Any feedback?
Information on EC 1.4.3.21 - primary-amine oxidase and Organism(s) Arthrobacter globiformis and UniProt Accession P46881
for references in articles please use BRENDA:EC1.4.3.21Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.4.3.21 primary-amine oxidaseIUBMB Comments
A group of enzymes that oxidize primary monoamines but have little or no activity towards diamines, such as histamine, or towards secondary and tertiary amines. They are copper quinoproteins (2,4,5-trihydroxyphenylalanine quinone) and, unlike EC 1.4.3.4, monoamine oxidase, are sensitive to inhibition by carbonyl-group reagents, such as semicarbazide. In some mammalian tissues the enzyme also functions as a vascular-adhesion protein (VAP-1).
Specify your search results
Word Map
- 1.4.3.21
- endothelial
- diamine
-
1.4.3.6
-
ssaos
-
deamination
- polyamines
- leukocyte
- putrescine
- lymphocyte
- spermine
- methylamine
-
lysyl
- vessel
- arthrobacter
-
extravasation
- phenylhydrazine
-
2,4,5-trihydroxyphenylalanine
- globiformis
- elastin
- cadaverine
-
klinman
-
biogenic
- aminoguanidine
-
half-reaction
- histaminase
- semiquinone
- pargyline
- acrolein
-
pyrroloquinoline
-
transmigration
- allylamine
- clorgyline
- beta-aminopropionitrile
- aminoacetone
-
copper-binding
-
self-processing
-
quinoproteins
- 2-phenylethylamine
-
addressins
- deprenyl
- phenelzine
- medicine
The taxonomic range for the selected organisms is: Arthrobacter globiformis
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
vap-1, vascular adhesion protein-1, copper amine oxidase, benzylamine oxidase, bovine serum amine oxidase, plasma amine oxidase, ssao/vap-1, bovine plasma amine oxidase, copper-containing amine oxidase, primary amine oxidase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
primary-amine:oxygen oxidoreductase (deaminating)
A group of enzymes that oxidize primary monoamines but have little or no activity towards diamines, such as histamine, or towards secondary and tertiary amines. They are copper quinoproteins (2,4,5-trihydroxyphenylalanine quinone) and, unlike EC 1.4.3.4, monoamine oxidase, are sensitive to inhibition by carbonyl-group reagents, such as semicarbazide. In some mammalian tissues the enzyme also functions as a vascular-adhesion protein (VAP-1).
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
2-phenylethylamine + H2O + O2
phenylacetaldehyde + NH3 + H2O2
-
-
-
?
histamine + H2O + O2
1H-imidazol-4-ylacetaldehyde + NH3 + H2O2
-
-
-
?
tyramine + H2O + O2
4-hydroxyphenylethanal + NH3 + H2O2
quantum mechanical hydrogen tunneling can be enhanced by an enzyme protein scaffold including the catalytic base that directly mediates the hydrogen transfer
-
-
?
2-phenylethylamine + H2O + O2
phenylacetaldehyde + NH3 + H2O2
-
preferred substrate
-
-
?
benzylamine + H2O + O2
benzaldehyde + NH3 + H2O2
-
very poor substrate
-
-
?
tyramine + H2O + O2
(4-hydroxyphenyl)acetaldehyde + NH3 + H2O2
-
preferred substrate
-
-
?
2-phenylethylamine + H2O + O2
2-phenylethanal + NH3 + H2O2
-
-
-
?
2-phenylethylamine + H2O + O2
2-phenylethanal + NH3 + H2O2
-
-
-
-
?
2-phenylethylamine + H2O + O2
2-phenylethanal + NH3 + H2O2
-
-
-
?
2-phenylethylamine + H2O + O2
2-phenylethanal + NH3 + H2O2
-
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2,4,5-trihydroxyphenylalaninequinone
i.e. TPQ cofactor, the cofactor is spontaneously formed by post-translational modifications of active site amino-acid residues
L-topaquinone
each subunit of the homodimer contains a protein-derived quinone cofactor, topaquinone. The reduced cofactor formed in the initial reductive half-reaction has two distinct conformations: a semiquinone radical form (TPQsq), in which the 4-hydroxyl group of the cofactor is ligated axially to the copper center, and an aminoresorcinol form (TPQamr), in which the cofactor has no direct contact with the copper. In crystallo thermodynamic analysis of the conformational change of the topaquinone cofactor in the copper amine oxidase
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
copper
Cu2+
Ni2+
Zn2+
besides Cu2+ ion, some divalent metal ions such as Co2+, Ni2+, and Zn2+ are also bound to the metal site of the apoenzyme so tightly that they are not replaced by excess Cu2+ ions added subsequently
Co2+
enzyme reconstituted with Co2+ exhibits 2.2% of the activity of the original Cu2+ -enzyme, KM-values for amine substrate and dioxygen are comparable
Co2+
besides Cu2+ ion, some divalent metal ions such as Co2+, Ni2+, and Zn2+ are also bound to the metal site of the apoenzyme so tightly that they are not replaced by excess Cu2+ ions added subsequently. Although these noncupric metal ions can not initiate topaquinone formation under the atmospheric conditions, slow spectral changes are observed in the enzyme bound with Co2+ or Ni2+ ion under the dioxygen-saturating conditions. X-ray crystallographic analysis reveals structural identity of the active sites of Co- and Ni-activated enzymes with Cu-enzyme. Co2+ and Ni2+ ions are also capable of forming topaquinone, though much less efficiently than Cu2+
Cu2+
copper protein. The native Cu2+ has essential roles such as catalyzing the electron transfer between the aminoresorcinol form of the reduced topaquinone cofactor and dioxygen, in part by providing a binding site for 1e- and 2e- reduced dioxygen species to be efficiently protonated and released and also preventing the back reaction between the product aldehyde and the aminoresorcinol form of the reduced topaquinone cofactor and dioxygen
Cu2+
besides Cu2+ ion, some divalent metal ions such as Co2+, Ni2+, and Zn2+ are also bound to the metal site of the apoenzyme so tightly that they are not replaced by excess Cu2+ ions added subsequently. Although these noncupric metal ions can not initiate topaquinone formation under the atmospheric conditions, slow spectral changes are observed in the enzyme bound with Co2+ or Ni2+ ion under the dioxygen-saturating conditions. X-ray crystallographic analysis reveals structural identity of the active sites of Co- and Ni-activated enzymes with Cu-enzyme. Co2+ and Ni2+ ions are also capable of forming topaquinone, though much less efficiently than Cu2+
Ni2+
enzyme reconstituted with Co2+ exhibits 0.9% of the activity of the original Cu2+ -enzyme, KM-values for amine substrate and dioxygen are comparable
Ni2+
besides Cu2+ ion, some divalent metal ions such as Co2+, Ni2+, and Zn2+ are also bound to the metal site of the apoenzyme so tightly that they are not replaced by excess Cu2+ ions added subsequently. Although these noncupric metal ions can not initiate topaquinone formation under the atmospheric conditions, slow spectral changes are observed in the enzyme bound with Co2+ or Ni2+ ion under the dioxygen-saturating conditions. X-ray crystallographic analysis reveals structural identity of the active sites of Co- and Ni-activated enzymes with Cu-enzyme. Co2+ and Ni2+ ions are also capable of forming topaquinone, though much less efficiently than Cu2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
benzylhydrazine
forms adducts with the TPQ cofactor, binding structure, overview
Br-
uncompetitive inhibitor with respect to the substrate amine and noncompetitive inhibitor with respect to dissolved oxygen
Cl-
uncompetitive inhibitor with respect to the substrate amine and noncompetitive inhibitor with respect to dissolved oxygen
F-
uncompetitive inhibitor with respect to the substrate amine and noncompetitive inhibitor with respect to dissolved oxygen
I-
uncompetitive inhibitor with respect to the substrate amine and noncompetitive inhibitor with respect to dissolved oxygen
ruthenium(II) molecular wires
the enzyme is reversibly inhibited by molecular wires comprising a Ru(II) complex head group and an aromatic tail group joined by an alkane linker
-
tranylcypromine
forms adducts with the TPQ cofactor, also termed (1R,2S)-rel-2-phenylcyclopropanamine, is a mixture of (1R,2S)-2-phenylcyclopropanamine and (1S,2R)-2-phenylcyclopropanamine, binding structure, overview
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0019
2-Phenylethylamine
pH 6.8, 30°C, Co2+-substituted enzyme
0.0025
2-Phenylethylamine
pH 6.8, 30°C, native copper protein
0.0038
2-Phenylethylamine
pH 6.8, 30°C, Ni2+-substituted enzyme
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.51
2-Phenylethylamine
pH 6.8, 30°C, Co2+-substituted enzyme
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
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). PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging-drop vapor diffusion method. Crystal structures of a series of Ru(II)-wire-enzyme complexes differing with respect to the length of the alkane linker
holenzyme, in which topaquinone is generated by incubation with Co2+ or Ni2+ and apoenzyme are crystallized by microdialysis method
microdialysis using 1.05 M potassium-sodium tartrate in 25 mM HEPES buffer, pH 6.8 containing 45% (v/v) glycerol
purified recombinant C-terminal StrepII-tagged enzyme in complex with inhibitors benzylhydrazine or tranylcypromine, vapour diffusion in hanging drop method, mixing of protein solution containing about 10 mg/ml protein in 50 mM HEPES, pH 7.0, with well solution containing 1.6 M ammonium sulfate and 150 mM sodium citrate pH 7.0. CuSO4, in a twofold molar excess, 2 weeks. The crystals are then transferred to a sitting drop well solution containing 30% v/v glycerol and 2 mM benzylhydrazine dihydrochloride or 0.4 mM tranylcypromine for 30 min, X-ray diffraction structure determination and analysis at 1.65-1.86 A resolution
X-ray crystal structures of the Co2+ and Ni2+-enzyme are solved at 2.0-1.8 A resolution
complexed with benzylhydrazine, 4-hydroxybenzylhydrazine and phenylhydrazine, micro dialysis method, using 1.05 M potassium sodium tartrate in 25mM HEPES buffer, pH 6.8, at 16°C
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D298A
Km-value for 2-phenylethylamine is 85% of the wild-type enzyme, kcat for 2-phenylethylamine is 360000fold lower than wild-type enzyme
D298K
in contrast to M602K and wild-type enzyme, the quinone in D298K does not react with any of the hydrazines. D298K shows no activity toward oxidative deamination of 2-phenylethylamine. The quinone formed in D298K is trapped in a conformation that can not react with amines. D298K contains a quinone other than topaquinone
M602K
the mutant enzyme shows 20% activity toward 2-phenylethylamine in comparison to wild-type enzyme
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kishishita, S.; Okajima, T.; Kim, M.; Yamaguchi, H.; Hirota, S.; Suzuki, S.; Kuroda, S.; Tanizawa, K.; Mure, M.
Role of copper ion in bacterial copper amine oxidase: spectroscopic and crystallographic studies of metal-substituted enzymes
J. Am. Chem. Soc.
125
1041-1055
2003
Arthrobacter globiformis (P46881), Arthrobacter globiformis
Murakawa, T.; Okajima, T.; Kuroda, S.; Nakamoto, T.; Taki, M.; Yamamoto, Y.; Hayashi, H.; Tanizawa, K.
Quantum mechanical hydrogen tunneling in bacterial copper amine oxidase reaction
Biochem. Biophys. Res. Commun.
342
414-423
2006
Arthrobacter globiformis (P46881)
Okajima, T.; Kishishita, S.; Chiu, Y.C.; Murakawa, T.; Kim, M.; Yamaguchi, H.; Hirota, S.; Kuroda, S.; Tanizawa, K.
Reinvestigation of metal ion specificity for quinone cofactor biogenesis in bacterial copper amine oxidase
Biochemistry
44
12041-12048
2005
Arthrobacter globiformis (P46881), Arthrobacter globiformis
Chiu, Y.C.; Okajima, T.; Murakawa, T.; Uchida, M.; Taki, M.; Hirota, S.; Kim, M.; Yamaguchi, H.; Kawano, Y.; Kamiya, N.; Kuroda, S.; Hayashi, H.; Yamamoto, Y.; Tanizawa, K.
Kinetic and structural studies on the catalytic role of the aspartic acid residue conserved in copper amine oxidase
Biochemistry
45
4105-4120
2006
Arthrobacter globiformis (P46881), Arthrobacter globiformis
Moore, R.H.; Spies, M.A.; Culpepper, M.B.; Murakawa, T.; Hirota, S.; Okajima, T.; Tanizawa, K.; Mure, M.
Trapping of a dopaquinone intermediate in the TPQ cofactor biogenesis in a copper-containing amine oxidase from Arthrobacter globiformis
J. Am. Chem. Soc.
129
11524-11534
2007
Arthrobacter globiformis (P46881), Arthrobacter globiformis
Langley, D.B.; Brown, D.E.; Cheruzel, L.E.; Contakes, S.M.; Duff, A.P.; Hilmer, K.M.; Dooley, D.M.; Gray, H.B.; Guss, J.M.; Freeman, H.C.
Enantiomer-specific binding of ruthenium(II) molecular wires by the amine oxidase of Arthrobacter globiformis
J. Am. Chem. Soc.
130
8069-8078
2008
Arthrobacter globiformis (P46881), Arthrobacter globiformis
Langley, D.B.; Trambaiolo, D.M.; Duff, A.P.; Dooley, D.M.; Freeman, H.C.; Guss, J.M.
Complexes of the copper-containing amine oxidase from Arthrobacter globiformis with the inhibitors benzylhydrazine and tranylcypromine
Acta Crystallogr. Sect. F
64
577-583
2008
Arthrobacter globiformis (P46881), Arthrobacter globiformis
Murakawa, T.; Hayashi, H.; Taki, M.; Yamamoto, Y.; Kawano, Y.; Tanizawa, K.; Okajima, T.
Structural insights into the substrate specificity of bacterial copper amine oxidase obtained by using irreversible inhibitors
J. Biochem.
151
167-178
2012
Arthrobacter globiformis
Murakawa, T.; Hamaguchi, A.; Nakanishi, S.; Kataoka, M.; Nakai, T.; Kawano, Y.; Yamaguchi, H.; Hayashi, H.; Tanizawa, K.; Okajima, T.
probing the catalytic mechanism of copper amine oxidase from Arthrobacter globiformis with halide ions
J. Biol. Chem.
290
23094-23109
2015
Arthrobacter globiformis (P46881), Arthrobacter globiformis
Murakawa, T.; Baba, S.; Kawano, Y.; Hayashi, H.; Yano, T.; Kumasaka, T.; Yamamoto, M.; Tanizawa, K.; Okajima, T.
In crystallo thermodynamic analysis of conformational change of the topaquinone cofactor in bacterial copper amine oxidase
Proc. Natl. Acad. Sci. USA
116
135-140
2019
Arthrobacter globiformis (P46881), Arthrobacter globiformis
EXTERNAL LINKS (specific for EC-Number 1.4.3.21)
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
