EzCatDB: M00202
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DB codeM00202
CATH domainDomain 1-.-.-.-
Domain 23.10.450.40 : Nuclear Transport Factor 2; Chain
Domain 33.10.450.40 : Nuclear Transport Factor 2; Chain
Domain 42.70.98.20 : 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,T00206,T00250,T00251
3.10.450.40 : Nuclear Transport Factor 2; ChainM00103,T00206,T00250,T00251

Enzyme Name
UniProtKBKEGG

Q16853
Protein nameMembrane primary 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
Copper amine oxidase
Semicarbazide-sensitive amine oxidase
SSAO
Vascular adhesion protein 1
VAP-1
HPAO
RefSeqNP_001264660.1 (Protein)
NM_001277731.1 (DNA/RNA sequence)
NP_001264661.1 (Protein)
NM_001277732.1 (DNA/RNA sequence)
NP_003725.1 (Protein)
NM_003734.3 (DNA/RNA sequence)
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 NumberQ16853
Entry nameAOC3_HUMAN
ActivityRCH(2)NH(2) + H(2)O + O(2) = RCHO + NH(3) + H(2)O(2).
SubunitHomodimer, disulfide-linked.
Subcellular locationMembrane, Single-pass type II membrane protein.
CofactorBinds 1 copper ion per subunit.,Binds 2 calcium ions per subunit.,Contains 1 topaquinone per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProductsintermediates
KEGG-idC00070C00076L00003C00375C00001C00007C00071C00014C00027I00021
I00022I00023I00024
CompoundCopperCalciumTopaquinoneRCH2NH2H2OOxygenAldehydeNH3H2O2Substrate Schiff-base (Iminoquinone=substrate)Carbanionic intermediateProduct Schiff-base (Aminoquinol=product)Aminoquinol/SemiquinoneIminoquinone
Typeheavy metaldivalent metal (Ca2+, Mg2+)amino acids,aromatic ring (only carbon atom)amine groupH2Ootherscarbohydrateamine group,organic ionothers




ChEBI28694
30052
29108
36077
68431

15377
27140
26689
15379

16134
16240





PubChem23978
271


962
22247451
977

222
784
22326046





                      
1pu4A01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
1pu4B01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
1us1A01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
1us1B01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
2c10A01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
2c10B01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
2c10C01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
2c10D01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
2c11A01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
2c11B01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
2c11C01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
2c11D01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
1pu4A02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
1pu4B02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
1us1A02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
1us1B02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
2c10A02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
2c10B02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
2c10C02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
2c10D02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
2c11A02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
2c11B02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
2c11C02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
2c11D02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound    
1pu4A03Bound:_CUBound:2x_CABound:TPQUnbound UnboundUnboundUnboundUnboundUnbound    
1pu4B03Bound:_CUBound:2x_CABound:TPQUnbound UnboundUnboundUnboundUnboundUnbound    
1us1A03Bound:_CUBound:2x_CABound:TPQUnbound UnboundUnboundUnboundUnboundUnbound    
1us1B03Bound:_CUBound:2x_CABound:TPQUnbound UnboundUnboundUnboundUnboundUnbound    
2c10A03Bound:_CUBound:2x_CABound:TPQUnbound UnboundUnboundUnboundUnboundUnbound    
2c10B03Bound:_CUBound:2x_CABound:TPQUnbound UnboundUnboundUnboundUnboundUnbound    
2c10C03Bound:_CUBound:2x_CABound:TPQUnbound UnboundUnboundUnboundUnboundUnbound    
2c10D03Bound:_CUBound:2x_CABound:TPQUnbound UnboundUnboundUnboundUnboundUnbound    
2c11A03Bound:_CU 1737Bound:2x_CAAnalogue:PAQUnbound UnboundUnboundUnboundUnboundIntermediate-analogue:PAQ    
2c11B03Bound:_CU 1742Bound:2x_CAAnalogue:PAQUnbound UnboundUnboundUnboundUnboundIntermediate-analogue:PAQ    
2c11C03Bound:_CU 1738Bound:2x_CAAnalogue:PAQUnbound UnboundUnboundUnboundUnboundIntermediate-analogue:PAQ    
2c11D03Bound:_CU 1742Bound:2x_CAAnalogue:PAQUnbound UnboundUnboundUnboundUnboundIntermediate-analogue:PAQ    

Active-site residues
resource
Swiss-prot;Q43077, P12807, P46881
pdbCatalytic residuesCofactor-binding residuesModified residues
           
1pu4A01 
 
 
1pu4B01 
 
 
1us1A01 
 
 
1us1B01 
 
 
2c10A01 
 
 
2c10B01 
 
 
2c10C01 
 
 
2c10D01 
 
 
2c11A01 
 
 
2c11B01 
 
 
2c11C01 
 
 
2c11D01 
 
 
1pu4A02 
 
 
1pu4B02 
 
 
1us1A02 
 
 
1us1B02 
 
 
2c10A02 
 
 
2c10B02 
 
 
2c10C02 
 
 
2c10D02 
 
 
2c11A02 
 
 
2c11B02 
 
 
2c11C02 
 
 
2c11D02 
 
 
1pu4A03TYR 372;ASP 386
HIS 520;HIS 522;HIS 684(Copper);ASP 529;LEU 530;ASP 531;ASP 673;LEU 674(Calcium-1);GLU 572;LYS 638;PHE 663;ASN 665;GLU 667(Calcium-2)
TPQ  471
1pu4B03TYR 372;ASP 386
HIS 520;HIS 522;HIS 684(Copper);ASP 529;LEU 530;ASP 531;ASP 673;LEU 674(Calcium-1);GLU 572;LYS 638;PHE 663;ASN 665;GLU 667(Calcium-2)
TPQ  471
1us1A03TYR 372;ASP 386
HIS 520;HIS 522;HIS 684(Copper);ASP 529;LEU 530;ASP 531;ASP 673;LEU 674(Calcium-1);GLU 572;LYS 638;PHE 663;ASN 665;GLU 667(Calcium-2)
TPQ  471
1us1B03TYR 372;ASP 386
HIS 520;HIS 522;HIS 684(Copper);ASP 529;LEU 530;ASP 531;ASP 673;LEU 674(Calcium-1);GLU 572;LYS 638;PHE 663;ASN 665;GLU 667(Calcium-2)
TPQ  471
2c10A03TYR 372;ASP 386
HIS 520;HIS 522;HIS 684(Copper);ASP 529;LEU 530;ASP 531;ASP 673;LEU 674(Calcium-1);GLU 572;LYS 638;PHE 663;ASN 665;GLU 667(Calcium-2)
TPQ  471
2c10B03TYR 372;ASP 386
HIS 520;HIS 522;HIS 684(Copper);ASP 529;LEU 530;ASP 531;ASP 673;LEU 674(Calcium-1);GLU 572;LYS 638;PHE 663;ASN 665;GLU 667(Calcium-2)
TPQ  471
2c10C03TYR 372;ASP 386
HIS 520;HIS 522;HIS 684(Copper);ASP 529;LEU 530;ASP 531;ASP 673;LEU 674(Calcium-1);GLU 572;LYS 638;PHE 663;ASN 665;GLU 667(Calcium-2)
TPQ  471
2c10D03TYR 372;ASP 386
HIS 520;HIS 522;HIS 684(Copper);ASP 529;LEU 530;ASP 531;ASP 673;LEU 674(Calcium-1);GLU 572;LYS 638;PHE 663;ASN 665;GLU 667(Calcium-2)
TPQ  471
2c11A03TYR 372;ASP 386
HIS 520;HIS 522;HIS 684(Copper);ASP 529;LEU 530;ASP 531;ASP 673;LEU 674(Calcium-1);GLU 572;LYS 638;PHE 663;ASN 665;GLU 667(Calcium-2)
PAQ 1729
2c11B03TYR 372;ASP 386
HIS 520;HIS 522;HIS 684(Copper);ASP 529;LEU 530;ASP 531;ASP 673;LEU 674(Calcium-1);GLU 572;LYS 638;PHE 663;ASN 665;GLU 667(Calcium-2)
PAQ 1729
2c11C03TYR 372;ASP 386
HIS 520;HIS 522;HIS 684(Copper);ASP 529;LEU 530;ASP 531;ASP 673;LEU 674(Calcium-1);GLU 572;LYS 638;PHE 663;ASN 665;GLU 667(Calcium-2)
PAQ 1729
2c11D03TYR 372;ASP 386
HIS 520;HIS 522;HIS 684(Copper);ASP 529;LEU 530;ASP 531;ASP 673;LEU 674(Calcium-1);GLU 572;LYS 638;PHE 663;ASN 665;GLU 667(Calcium-2)
PAQ 1729

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Fig.2, p.1725-1728
[2]Scheme 1, Scheme 2, p.10965-10967, p.10972-10976
[3]p.1966-1970
[4]Fig.3, p.1555-1556, p.1558-1560

references
[1]
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
[2]
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
[3]
PubMed ID16046623
JournalProtein Sci
Year2005
Volume14
Pages1964-74
AuthorsAirenne TT, Nymalm Y, Kidron H, Smith DJ, Pihlavisto M, Salmi M, Jalkanen S, Johnson MS, Salminen TA
TitleCrystal structure of the human vascular adhesion protein-1: unique structural features with functional implications.
Related PDB1pu4,1us1
Related UniProtKBQ16853
[4]
PubMed ID16239734
JournalActa Crystallogr D Biol Crystallogr
Year2005
Volume61
Pages1550-62
AuthorsJakobsson E, Nilsson J, Ogg D, Kleywegt GJ
TitleStructure of human semicarbazide-sensitive amine oxidase/vascular adhesion protein-1.
Related PDB2c10,2c11

comments
The catalytic domain of this enzyme is homologous to those of counterpart enzymes from E. coli (M00103 in EzCatDB), from bovine (T00251 in EzCatDB), and from pea (T00250 in EzCatDB).
Cofactor, topaquinone (2,4,5-trihydroxyphenylalanine), is a modified residue, generated from active site tyrosine residue (Tyr471) by self-catalysis (see [6] of M00103 in EzCatDB).
Although this enzyme binds a copper ion and two calcium ions as cofactors per subunit, the calcium ions are not involved in catalysis.
According to the literature [1] and [2] (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
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
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)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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