EzCatDB: T00250
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DB codeT00250
CATH domainDomain 13.10.450.40 : Nuclear Transport Factor 2; Chain
Domain 23.10.450.40 : Nuclear Transport Factor 2; Chain
Domain 32.70.98.20 : Beta-galactosidase; Chain A, domain 5Catalytic domain
E.C.1.4.3.21

CATH domainRelated DB codes (homologues)
2.70.98.20 : Beta-galactosidase; Chain A, domain 5M00103,M00202,T00206,T00251
3.10.450.40 : Nuclear Transport Factor 2; ChainM00103,M00202,T00206,T00251

Enzyme Name
UniProtKBKEGG

Q43077
Protein namePrimary amine oxidaseprimary-amine oxidase
amine oxidase (ambiguous)
amine oxidase (copper-containing)
amine oxidase (pyridoxal containing) (incorrect)
benzylamine oxidase (incorrect)
CAO (ambiguous)
copper amine oxidase (ambiguous)
Cu-amine oxidase (ambiguous)
Cu-containing amine oxidase (ambiguous)
diamine oxidase (incorrect)
diamino oxhydrase (incorrect)
histamine deaminase (ambiguous)
histamine oxidase (ambiguous)
monoamine oxidase (ambiguous)
plasma monoamine oxidase (ambiguous)
polyamine oxidase (ambiguous)
semicarbazide-sensitive amine oxidase (ambiguous)
SSAO (ambiguous)
SynonymsEC 1.4.3.21
Amine oxidase [copper-containing]
PfamPF01179 (Cu_amine_oxid)
PF02727 (Cu_amine_oxidN2)
PF02728 (Cu_amine_oxidN3)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00260Glycine, serine and threonine metabolism
MAP00350Tyrosine metabolism
MAP00360Phenylalanine metabolism
MAP00410beta-Alanine metabolism
MAP00960Alkaloid biosynthesis II

UniProtKB:Accession NumberQ43077
Entry nameAMO_PEA
ActivityRCH(2)NH(2) + H(2)O + O(2) = RCHO + NH(3) + H(2)O(2).
SubunitHomodimer.
Subcellular location
CofactorBinds 1 copper ion per subunit.,Binds 1 manganese ion per subunit.,Contains 1 topaquinone per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProductsintermediates
KEGG-idC00070C00034L00003C00375C00001C00007C00071C00014C00027I00021
I00022I00023I00024
CompoundCopperManganeseTopaquinoneRCH2NH2H2OOxygenAldehydeNH3H2O2Substrate Schiff-base (Iminoquinone=substrate)Carbanionic intermediateProduct Schiff-base (Aminoquinol=product)Aminoquinol/SemiquinoneIminoquinone
Typeheavy metalheavy metalamino acids,aromatic ring (only carbon atom)amine groupH2Ootherscarbohydrateamine group,organic ionothers




ChEBI28694
30052
18291
35154
36077
68431

15377
27140
26689
15379

16134
16240





PubChem23978
23930


962
22247451
977

222
784
22326046





                      
1ksiA01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnbound     
1ksiB01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnbound     
1w2zA01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnbound     
1w2zB01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnbound     
1w2zC01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnbound     
1w2zD01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnbound     
1ksiA02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnbound     
1ksiB02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnbound     
1w2zA02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnbound     
1w2zB02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnbound     
1w2zC02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnbound     
1w2zD02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnbound     
1ksiA03Bound:_CUBound:_MNBound:TPQUnbound UnboundUnboundUnboundUnbound     
1ksiB03Bound:_CUBound:_MNBound:TPQUnbound UnboundUnboundUnboundUnbound     
1w2zA03Bound:_CUBound:_MNBound:TPQUnbound UnboundUnboundUnboundUnbound     
1w2zB03Bound:_CUBound:_MNBound:TPQUnbound UnboundUnboundUnboundUnbound     
1w2zC03Bound:_CUBound:_MNBound:TPQUnbound UnboundUnboundUnboundUnbound     
1w2zD03Bound:_CUBound:_MNBound:TPQUnbound UnboundUnboundUnboundUnbound     

Active-site residues
pdbCatalytic residuesCofactor-binding residuesModified residues
           
1ksiA01 
 
 
1ksiB01 
 
 
1w2zA01 
 
 
1w2zB01 
 
 
1w2zC01 
 
 
1w2zD01 
 
 
1ksiA02 
 
 
1ksiB02 
 
 
1w2zA02 
 
 
1w2zB02 
 
 
1w2zC02 
 
 
1w2zD02 
 
 
1ksiA03TYR 286;ASP 300
HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese)
TPQ 387
1ksiB03TYR 286;ASP 300
HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese)
TPQ 387
1w2zA03TYR 286;ASP 300
HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese)
TPQ 387
1w2zB03TYR 286;ASP 300
HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese)
TPQ 387
1w2zC03TYR 286;ASP 300
HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese)
TPQ 387
1w2zD03TYR 286;ASP 300
HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese)
TPQ 387

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Scheme 1
[2]Fig.3, p.263
[5]Scheme 1, p.16375-16376
[6]Fig.1, p.943-948
[7]Fig.2, p.1725-1728
[8]Fig.7, p.1431-1432
[10]Scheme 1, p.3652-3655
[11]Scheme 1, Scheme 2, p.10965-10967, p.10972-10976
[12]Fig.2, Fig.5, p.4000-4006
[13]p.599-602

references
[1]
PubMed ID2016294
JournalJ Biol Chem
Year1991
Volume266
Pages6795-800
AuthorsColeman AA, Scaman CH, Kang YJ, Palcic MM
TitleStereochemical trends in copper amine oxidase reactions.
[2]
PubMed ID1846226
JournalNature
Year1991
Volume349
Pages262-4
AuthorsDooley DM, McGuirl MA, Brown DE, Turowski PN, McIntire WS, Knowles PF
TitleA Cu(I)-semiquinone state in substrate-reduced amine oxidases.
[3]
PubMed ID1310034
JournalBiochemistry
Year1992
Volume31
Pages8-12
AuthorsPedersen JZ, el-Sherbini S, Finazzi-Agro A, Rotilio G
TitleA substrate-cofactor free radical intermediate in the reaction mechanism of copper amine oxidase.
[4]
PubMed ID7824646
JournalPlant Physiol
Year1994
Volume106
Pages1205-11
AuthorsMcGuirl MA, McCahon CD, McKeown KA, Dooley DM
TitlePurification and characterization of pea seedling amine oxidase for crystallization studies.
[5]
PubMed ID8845363
JournalBiochemistry
Year1995
Volume34
Pages16375-81
AuthorsMedda R, Padiglia A, Pedersen JZ, Rotilio G, Finazzi Agro A, Floris G
TitleThe reaction mechanism of copper amine oxidase: detection of intermediates by the use of substrates and inhibitors.
[6]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS)
Medline ID96398683
PubMed ID8805580
JournalStructure
Year1996
Volume4
Pages943-55
AuthorsKumar V, Dooley DM, Freeman HC, Guss JM, Harvey I, McGuirl MA, Wilce MC, Zubak VM
TitleCrystal structure of a eukaryotic (pea seedling) copper-containing amine oxidase at 2.2 A resolution.
Related PDB1ksi
Related UniProtKBQ43077
[7]
CommentsX-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS)
Medline ID20045000
PubMed ID10576737
JournalScience
Year1999
Volume286
Pages1724-8
AuthorsWilmot CM, Hajdu J, McPherson MJ, Knowles PF, Phillips SE
TitleVisualization of dioxygen bound to copper during enzyme catalysis.
Related PDB1d6u,1d6y,1d6z
Related UniProtKBP46883
[8]
PubMed ID10691980
JournalEur J Biochem
Year2000
Volume267
Pages1423-33
AuthorsFrebort I, Sebela M, Svendsen I, Hirota S, Endo M, Yamauchi O, Bellelli A, Lemr K, Pec P
TitleMolecular mode of interaction of plant amine oxidase with the mechanism-based inhibitor 2-butyne-1,4-diamine.
[9]
PubMed ID11846789
JournalEur J Biochem
Year2002
Volume269
Pages884-92
AuthorsAscenzi P, Fasano M, Marino M, Venturini G, Federico R
TitleAgmatine oxidation by copper amine oxidase.
[10]
PubMed ID12153561
JournalEur J Biochem
Year2002
Volume269
Pages3645-58
AuthorsShepard EM, Smith J, Elmore BO, Kuchar JA, Sayre LM, Dooley DM
TitleTowards the development of selective amine oxidase inhibitors. Mechanism-based inhibition of six copper containing amine oxidases.
[11]
CommentsX-ray crystallography
PubMed ID15323556
JournalBiochemistry
Year2004
Volume43
Pages10965-78
AuthorsO'Connell KM, Langley DB, Shepard EM, Duff AP, Jeon HB, Sun G, Freeman HC, Guss JM, Sayre LM, Dooley DM
TitleDifferential inhibition of six copper amine oxidases by a family of 4-(aryloxy)-2-butynamines: evidence for a new mode of inactivation.
Related PDB1sih,1sii
[12]
PubMed ID15038754
JournalJ Am Chem Soc
Year2004
Volume126
Pages3996-4006
AuthorsPrabhakar R, Siegbahn PE
TitleA theoretical study of the mechanism for the biogenesis of cofactor topaquinone in copper amine oxidases.
[13]
CommentsX-ray crystallography
PubMed ID15533431
JournalJ Mol Biol
Year2004
Volume344
Pages599-607
AuthorsDuff AP, Trambaiolo DM, Cohen AE, Ellis PJ, Juda GA, Shepard EM, Langley DB, Dooley DM, Freeman HC, Guss JM
TitleUsing xenon as a probe for dioxygen-binding sites in copper amine oxidases.
Related PDB1w2z,1rjo

comments
The catalytic domain of this enzyme is homologous to those of counterpart enzymes from E. coli (M00103 in EzCatDB), and from bovine (T00251 in EzCatDB).
Cofactor, topaquinone (2,4,5-trihydroxyphenylalanine), is a modified residue, generated from active site tyrosine residue (Tyr466) by self-catalysis (see [6] of M00103 in EzCatDB).
Although this enzyme binds a copper ion and a manganese ion as cofactors per subunit, the manganese ion is not involved in catalysis.
According to the literature [6] and [7] (for its homologue), this enzyme catalyzes two half-reactions: (I) reductive half-reaction, and (II) oxidative half-reaction. These half-reactions can be subdivided into several basic reactions in terms of RLCP classification.
(I) Reductive half-reaction:
(A) Exchange of double-bonded atoms; Schiff-base formation; Substrate amine forms a Schiff-base with topaquinone, generating iminoquinone=substrate and H2O (dehydration):
(B) Isomerization from iminoquinone=substrate complex to aminoquinol=product complex (through a carbanionic intermediate):
(C) Exchange of double-bonded atoms; Schiff-base deformation; H2O reacts with the intermediate, generating aminoquinol and product aldehyde (hydration):
(II) Oxidative half-reaction:
(D) Reduction of dioxygen (O2) by aminoquinol, to produce hydrogen peroxide (H2O2) and iminoquinone (Hydride transfer):
(E) Exchange of double-bonded atoms; Schiff-base deformation; H2O reacts with the intermediate, generating topaquinone and product ammonia (hydration):

createdupdated
2005-05-262009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
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Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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