DB code: T00250

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 T00251
3.10.450.40 : Nuclear Transport Factor 2; Chain M00103 M00202 T00206 T00251

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
Q43077 Primary amine oxidase
EC 1.4.3.21
Amine oxidase [copper-containing]
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
Q43077 AMO_PEA RCH(2)NH(2) + H(2)O + O(2) = RCHO + NH(3) + H(2)O(2). Homodimer. Binds 1 copper ion per subunit. Binds 1 manganese ion 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 C00034 L00003 C00375 C00001 C00007 C00071 C00014 C00027 I00021 I00022 I00023 I00024
E.C.
Compound Copper Manganese 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 heavy metal amino acids,aromatic ring (only carbon atom) amine group H2O others carbohydrate amine group,organic ion others
ChEBI 28694
 30052
 28694
 30052
 		18291
 35154
 18291
 35154
 		36077
 68431
 36077
 68431
 		15377
 15377
 		15379
 26689
 27140
 15379
 26689
 27140
 		16134
 16134
 		16240
 16240
PubChem 23978
 23978
 		23930
 23930
 		22247451
 962
 22247451
 962
 		977
 977
 		222
 222
 		22326046
 784
 22326046
 784
1ksiA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ksiB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w2zA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w2zB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w2zC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w2zD01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ksiA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ksiB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w2zA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w2zB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w2zC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w2zD02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ksiA03 Bound:_CU Bound:_MN Bound:TPQ Unbound Unbound Unbound Unbound Unbound
1ksiB03 Bound:_CU Bound:_MN Bound:TPQ Unbound Unbound Unbound Unbound Unbound
1w2zA03 Bound:_CU Bound:_MN Bound:TPQ Unbound Unbound Unbound Unbound Unbound
1w2zB03 Bound:_CU Bound:_MN Bound:TPQ Unbound Unbound Unbound Unbound Unbound
1w2zC03 Bound:_CU Bound:_MN Bound:TPQ Unbound Unbound Unbound Unbound Unbound
1w2zD03 Bound:_CU Bound:_MN Bound:TPQ Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ksiA01
1ksiB01
1w2zA01
1w2zB01
1w2zC01
1w2zD01
1ksiA02
1ksiB02
1w2zA02
1w2zB02
1w2zC02
1w2zD02
1ksiA03 TYR 286;ASP 300 HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese) TPQ 387
1ksiB03 TYR 286;ASP 300 HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese) TPQ 387
1w2zA03 TYR 286;ASP 300 HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese) TPQ 387
1w2zB03 TYR 286;ASP 300 HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese) TPQ 387
1w2zC03 TYR 286;ASP 300 HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese) TPQ 387
1w2zD03 TYR 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
References Sections No. 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]
Resource
Comments
Medline ID
PubMed ID 2016294
Journal J Biol Chem
Year 1991
Volume 266
Pages 6795-800
Authors Coleman AA, Scaman CH, Kang YJ, Palcic MM
Title Stereochemical trends in copper amine oxidase 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 1310034
Journal Biochemistry
Year 1992
Volume 31
Pages 8-12
Authors Pedersen JZ, el-Sherbini S, Finazzi-Agro A, Rotilio G
Title A substrate-cofactor free radical intermediate in the reaction mechanism of copper amine oxidase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 7824646
Journal Plant Physiol
Year 1994
Volume 106
Pages 1205-11
Authors McGuirl MA, McCahon CD, McKeown KA, Dooley DM
Title Purification and characterization of pea seedling amine oxidase for crystallization studies.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 8845363
Journal Biochemistry
Year 1995
Volume 34
Pages 16375-81
Authors Medda R, Padiglia A, Pedersen JZ, Rotilio G, Finazzi Agro A, Floris G
Title The reaction mechanism of copper amine oxidase: detection of intermediates by the use of substrates and inhibitors.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS)
Medline ID 96398683
PubMed ID 8805580
Journal Structure
Year 1996
Volume 4
Pages 943-55
Authors Kumar V, Dooley DM, Freeman HC, Guss JM, Harvey I, McGuirl MA, Wilce MC, Zubak VM
Title Crystal structure of a eukaryotic (pea seedling) copper-containing amine oxidase at 2.2 A resolution.
Related PDB 1ksi
Related UniProtKB Q43077
[7]
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
[8]
Resource
Comments
Medline ID
PubMed ID 10691980
Journal Eur J Biochem
Year 2000
Volume 267
Pages 1423-33
Authors Frebort I, Sebela M, Svendsen I, Hirota S, Endo M, Yamauchi O, Bellelli A, Lemr K, Pec P
Title Molecular mode of interaction of plant amine oxidase with the mechanism-based inhibitor 2-butyne-1,4-diamine.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 11846789
Journal Eur J Biochem
Year 2002
Volume 269
Pages 884-92
Authors Ascenzi P, Fasano M, Marino M, Venturini G, Federico R
Title Agmatine oxidation by copper amine oxidase.
Related PDB
Related UniProtKB
[10]
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
[11]
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
[12]
Resource
Comments
Medline ID
PubMed ID 15038754
Journal J Am Chem Soc
Year 2004
Volume 126
Pages 3996-4006
Authors Prabhakar R, Siegbahn PE
Title A theoretical study of the mechanism for the biogenesis of cofactor topaquinone in copper amine oxidases.
Related PDB
Related UniProtKB
[13]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 15533431
Journal J Mol Biol
Year 2004
Volume 344
Pages 599-607
Authors Duff AP, Trambaiolo DM, Cohen AE, Ellis PJ, Juda GA, Shepard EM, Langley DB, Dooley DM, Freeman HC, Guss JM
Title Using xenon as a probe for dioxygen-binding sites in copper amine oxidases.
Related PDB 1w2z 1rjo
Related UniProtKB

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):

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