DB code: M00202

CATH domain -.-.-.- :
3.10.450.40 : Nuclear Transport Factor 2; Chain
3.10.450.40 : Nuclear Transport Factor 2; Chain
2.70.98.20 : Beta-galactosidase; Chain A, domain 5 Catalytic domain
E.C. 1.4.3.21
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.70.98.20 : Beta-galactosidase; Chain A, domain 5 M00103 T00206 T00250 T00251
3.10.450.40 : Nuclear Transport Factor 2; Chain M00103 T00206 T00250 T00251

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q16853 Membrane primary amine oxidase
EC 1.4.3.21
Copper amine oxidase
Semicarbazide-sensitive amine oxidase
SSAO
Vascular adhesion protein 1
VAP-1
HPAO
NP_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)
PF01179 (Cu_amine_oxid)
PF02727 (Cu_amine_oxidN2)
PF02728 (Cu_amine_oxidN3)
[Graphical View]

KEGG enzyme name
primary-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)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q16853 AOC3_HUMAN RCH(2)NH(2) + H(2)O + O(2) = RCHO + NH(3) + H(2)O(2). Homodimer, disulfide-linked. Membrane, Single-pass type II membrane protein. Binds 1 copper ion per subunit. Binds 2 calcium ions per subunit. Contains 1 topaquinone per subunit.

KEGG Pathways
Map code Pathways E.C.
MAP00260 Glycine, serine and threonine metabolism
MAP00350 Tyrosine metabolism
MAP00360 Phenylalanine metabolism
MAP00410 beta-Alanine metabolism
MAP00960 Alkaloid biosynthesis II

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00070 C00076 L00003 C00375 C00001 C00007 C00071 C00014 C00027 I00021 I00022 I00023 I00024
E.C.
Compound Copper Calcium Topaquinone RCH2NH2 H2O Oxygen Aldehyde NH3 H2O2 Substrate Schiff-base (Iminoquinone=substrate) Carbanionic intermediate Product Schiff-base (Aminoquinol=product) Aminoquinol/Semiquinone Iminoquinone
Type heavy metal divalent metal (Ca2+, Mg2+) amino acids,aromatic ring (only carbon atom) amine group H2O others carbohydrate amine group,organic ion others
ChEBI 28694
 30052
 28694
 30052
 		29108
 29108
 		36077
 68431
 36077
 68431
 		15377
 15377
 		15379
 26689
 27140
 15379
 26689
 27140
 		16134
 16134
 		16240
 16240
PubChem 23978
 23978
 		271
 271
 		22247451
 962
 22247451
 962
 		977
 977
 		222
 222
 		22326046
 784
 22326046
 784
1pu4A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pu4B01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1us1A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1us1B01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c10A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c10B01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c10C01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c10D01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c11A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c11B01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c11C01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c11D01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pu4A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pu4B02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1us1A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1us1B02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c10A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c10B02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c10C02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c10D02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c11A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c11B02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c11C02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c11D02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pu4A03 Bound:_CU Bound:2x_CA Bound:TPQ Unbound Unbound Unbound Unbound Unbound Unbound
1pu4B03 Bound:_CU Bound:2x_CA Bound:TPQ Unbound Unbound Unbound Unbound Unbound Unbound
1us1A03 Bound:_CU Bound:2x_CA Bound:TPQ Unbound Unbound Unbound Unbound Unbound Unbound
1us1B03 Bound:_CU Bound:2x_CA Bound:TPQ Unbound Unbound Unbound Unbound Unbound Unbound
2c10A03 Bound:_CU Bound:2x_CA Bound:TPQ Unbound Unbound Unbound Unbound Unbound Unbound
2c10B03 Bound:_CU Bound:2x_CA Bound:TPQ Unbound Unbound Unbound Unbound Unbound Unbound
2c10C03 Bound:_CU Bound:2x_CA Bound:TPQ Unbound Unbound Unbound Unbound Unbound Unbound
2c10D03 Bound:_CU Bound:2x_CA Bound:TPQ Unbound Unbound Unbound Unbound Unbound Unbound
2c11A03 Bound:_CU_1737 Bound:2x_CA Analogue:PAQ Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:PAQ
2c11B03 Bound:_CU_1742 Bound:2x_CA Analogue:PAQ Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:PAQ
2c11C03 Bound:_CU_1738 Bound:2x_CA Analogue:PAQ Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:PAQ
2c11D03 Bound:_CU_1742 Bound:2x_CA Analogue:PAQ Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:PAQ

Reference for Active-site residues
resource references E.C.
Swiss-prot;Q43077, P12807, P46881

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1pu4A01
1pu4B01
1us1A01
1us1B01
2c10A01
2c10B01
2c10C01
2c10D01
2c11A01
2c11B01
2c11C01
2c11D01
1pu4A02
1pu4B02
1us1A02
1us1B02
2c10A02
2c10B02
2c10C02
2c10D02
2c11A02
2c11B02
2c11C02
2c11D02
1pu4A03 TYR 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
1pu4B03 TYR 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
1us1A03 TYR 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
1us1B03 TYR 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
2c10A03 TYR 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
2c10B03 TYR 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
2c10C03 TYR 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
2c10D03 TYR 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
2c11A03 TYR 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
2c11B03 TYR 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
2c11C03 TYR 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
2c11D03 TYR 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
References Sections No. 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]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS)
Medline ID 20045000
PubMed ID 10576737
Journal Science
Year 1999
Volume 286
Pages 1724-8
Authors Wilmot CM, Hajdu J, McPherson MJ, Knowles PF, Phillips SE
Title Visualization of dioxygen bound to copper during enzyme catalysis.
Related PDB 1d6u 1d6y 1d6z
Related UniProtKB P46883
[2]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 15323556
Journal Biochemistry
Year 2004
Volume 43
Pages 10965-78
Authors O'Connell KM, Langley DB, Shepard EM, Duff AP, Jeon HB, Sun G, Freeman HC, Guss JM, Sayre LM, Dooley DM
Title Differential inhibition of six copper amine oxidases by a family of 4-(aryloxy)-2-butynamines: evidence for a new mode of inactivation.
Related PDB 1sih 1sii
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 16046623
Journal Protein Sci
Year 2005
Volume 14
Pages 1964-74
Authors Airenne TT, Nymalm Y, Kidron H, Smith DJ, Pihlavisto M, Salmi M, Jalkanen S, Johnson MS, Salminen TA
Title Crystal structure of the human vascular adhesion protein-1: unique structural features with functional implications.
Related PDB 1pu4 1us1
Related UniProtKB Q16853
[4]
Resource
Comments
Medline ID
PubMed ID 16239734
Journal Acta Crystallogr D Biol Crystallogr
Year 2005
Volume 61
Pages 1550-62
Authors Jakobsson E, Nilsson J, Ogg D, Kleywegt GJ
Title Structure of human semicarbazide-sensitive amine oxidase/vascular adhesion protein-1.
Related PDB 2c10 2c11
Related UniProtKB

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):

Created Updated
2005-05-26 2009-02-26