DB code: T00251

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 M00202 T00206 T00250
3.10.450.40 : Nuclear Transport Factor 2; Chain M00103 M00202 T00206 T00250

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q29437 Primary amine oxidase, liver isozyme
EC 1.4.3.21
Copper amine oxidase
Amine oxidase [copper-containing]
Serum amine oxidase
SAO
NP_001124236.1 (Protein)
NM_001130764.1 (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
Q29437 AOCX_BOVIN RCH(2)NH(2) + H(2)O + O(2) = RCHO + NH(3) + H(2)O(2). Secreted, extracellular space. 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
1tu5A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1tu5B01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1tu5A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1tu5B02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1tu5A03 Bound:_CU Bound:2x_CA Bound:TPQ_470 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1tu5B03 Bound:_CU Bound:2x_CA Bound:TPQ_470 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

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
1tu5A01
1tu5B01
1tu5A02
1tu5B02
1tu5A03 TYR 371;ASP 385 HIS 519;HIS 521;HIS 683(Copper);ASP 528;LEU 529;ASP 530;ASP 672;LEU 673(Calcium-1);GLU 571;PHE 662;ASN 664;GLU 666(Calcium-2) TPQ 470 TPQ 2',4',5'-topaquinone
1tu5B03 TYR 371;ASP 385 HIS 519;HIS 521;HIS 683(Copper);ASP 528;LEU 529;ASP 530;ASP 672;LEU 673(Calcium-1);GLU 571;PHE 662;ASN 664;GLU 666(Calcium-2) TPQ 470 TPQ 2',4',5'-topaquinone

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
Fig.2, p.1725-1728
[5]
Scheme 1, p.3645,
[6]
Scheme 1, p.10966
[7]
p.995, p.997-1001

References
[1]
Resource
Comments
Medline ID
PubMed ID 2688201
Journal Trends Biochem Sci
Year 1989
Volume 14
Pages 368-73
Authors Klinman JP
Title Quantum mechanical effects in enzyme-catalysed hydrogen transfer reactions.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 1846226
Journal Nature
Year 1991
Volume 349
Pages 262-4
Authors Dooley DM, McGuirl MA, Brown DE, Turowski PN, McIntire WS, Knowles PF
Title A Cu(I)-semiquinone state in substrate-reduced amine oxidases.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 7791619
Journal Methods Enzymol
Year 1995
Volume 249
Pages 373-97
Authors Bahnson BJ, Klinman JP
Title Hydrogen tunneling in enzyme catalysis.
Related PDB
Related UniProtKB
[4]
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
[5]
Resource
Comments
Medline ID
PubMed ID 12153561
Journal Eur J Biochem
Year 2002
Volume 269
Pages 3645-58
Authors Shepard EM, Smith J, Elmore BO, Kuchar JA, Sayre LM, Dooley DM
Title Towards the development of selective amine oxidase inhibitors. Mechanism-based inhibition of six copper containing amine oxidases.
Related PDB
Related UniProtKB
[6]
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
[7]
Resource
Comments
Medline ID
PubMed ID 15701511
Journal J Mol Biol
Year 2005
Volume 346
Pages 991-1004
Authors Lunelli M, Di Paolo ML, Biadene M, Calderone V, Battistutta R, Scarpa M, Rigo A, Zanotti G
Title Crystal structure of amine oxidase from bovine serum.
Related PDB 1tu5
Related UniProtKB

Comments
The catalytic domain of this enzyme is homologous to amine oxidase from E. coli (M00103 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 two calcium ions as cofactors per subunit, the calcium ions are not involved in catalysis.
According to the literature [4] (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