T00250
type: Enzyme
cath: Nuclear Transport Factor 2; Chain
cath: Beta-galactosidase; Chain A, domain 5
ec: https://purl.uniprot.org/enzyme/1.4.3.21
uniprot: Q43077
kegg enzyme: primary-amine oxidase
kegg enzyme: amine oxidase (ambiguous)
kegg enzyme: amine oxidase (copper-containing)
kegg enzyme: amine oxidase (pyridoxal containing) (incorrect)
kegg enzyme: benzylamine oxidase (incorrect)
kegg enzyme: CAO (ambiguous)
kegg enzyme: copper amine oxidase (ambiguous)
kegg enzyme: Cu-amine oxidase (ambiguous)
kegg enzyme: Cu-containing amine oxidase (ambiguous)
kegg enzyme: diamine oxidase (incorrect)
kegg enzyme: diamino oxhydrase (incorrect)
kegg enzyme: histamine deaminase (ambiguous)
kegg enzyme: histamine oxidase (ambiguous)
kegg enzyme: monoamine oxidase (ambiguous)
kegg enzyme: plasma monoamine oxidase (ambiguous)
kegg enzyme: polyamine oxidase (ambiguous)
kegg enzyme: semicarbazide-sensitive amine oxidase (ambiguous)
kegg enzyme: SSAO (ambiguous)
kegg pathway: Glycine, serine and threonine metabolism
kegg pathway: Tyrosine metabolism
kegg pathway: Phenylalanine metabolism
kegg pathway: beta-Alanine metabolism
kegg pathway: Alkaloid biosynthesis II
kegg cofactor: Copper
kegg cofactor: Manganese
kegg cofactor: Topaquinone
kegg substrate: RCH2NH2
kegg substrate: H2O
kegg substrate: Oxygen
kegg product: Aldehyde
kegg product: NH3
kegg product: H2O2
kegg intermediate: Substrate Schiff-base (Iminoquinone=substrate)
kegg intermediate: Product Schiff-base (Aminoquinol=product)
kegg intermediate: Aminoquinol/Semiquinone
kegg intermediate: Iminoquinone
pdb: 1ksiA01
pdb: 1ksiB01
pdb: 1w2zA01
pdb: 1w2zB01
pdb: 1w2zC01
pdb: 1w2zD01
pdb: 1ksiA02
pdb: 1ksiB02
pdb: 1w2zA02
pdb: 1w2zB02
pdb: 1w2zC02
pdb: 1w2zD02
pdb: 1ksiA03
pdb: 1ksiB03
pdb: 1w2zA03
pdb: 1w2zB03
pdb: 1w2zC03
pdb: 1w2zD03
pdb bound state: Unbound
  compound: RCH2NH2
  pdb: 1ksiA01
pdb bound state: Unbound
  compound: RCH2NH2
  pdb: 1ksiB01
pdb bound state: Unbound
  compound: RCH2NH2
  pdb: 1w2zA01
pdb bound state: Unbound
  compound: RCH2NH2
  pdb: 1w2zB01
pdb bound state: Unbound
  compound: RCH2NH2
  pdb: 1w2zC01
pdb bound state: Unbound
  compound: RCH2NH2
  pdb: 1w2zD01
pdb bound state: Unbound
  compound: RCH2NH2
  pdb: 1ksiA02
references: Stereochemical trends in copper amine oxidase reactions.
references: A Cu(I)-semiquinone state in substrate-reduced amine oxidases.
references: A substrate-cofactor free radical intermediate in the reaction mechanism of copper amine oxidase.
references: Purification and characterization of pea seedling amine oxidase for crystallization studies.
references: The reaction mechanism of copper amine oxidase: detection of intermediates by the use of substrates and inhibitors.
references: Crystal structure of a eukaryotic (pea seedling) copper-containing amine oxidase at 2.2 A resolution.
references: Visualization of dioxygen bound to copper during enzyme catalysis.
references: Molecular mode of interaction of plant amine oxidase with the mechanism-based inhibitor 2-butyne-1,4-diamine.
references: Agmatine oxidation by copper amine oxidase.
references: Towards the development of selective amine oxidase inhibitors. Mechanism-based inhibition of six copper containing amine oxidases.
references: Differential inhibition of six copper amine oxidases by a family of 4-(aryloxy)-2-butynamines: evidence for a new mode of inactivation.
references: A theoretical study of the mechanism for the biogenesis of cofactor topaquinone in copper amine oxidases.
references: Using xenon as a probe for dioxygen-binding sites in copper amine oxidases.
comment: 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):

Nuclear Transport Factor 2; Chain
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.10.450.40

Beta-galactosidase; Chain A, domain 5
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/2.70.98.20
catalytic domain: index.html

Glycine, serine and threonine metabolism
type: KeggPathway
references: KEGG:MAP00260

Tyrosine metabolism
type: KeggPathway
references: KEGG:MAP00350

Phenylalanine metabolism
type: KeggPathway
references: KEGG:MAP00360

beta-Alanine metabolism
type: KeggPathway
references: KEGG:MAP00410

Alkaloid biosynthesis II
type: KeggPathway
references: KEGG:MAP00960

Copper
type: KeggCofactor
references: KEGG:C00070
compound type: heavy metal
references: CHEBI:28694
references: CHEBI:30052
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Manganese
type: KeggCofactor
references: KEGG:C00034
compound type: heavy metal
references: CHEBI:18291
references: CHEBI:35154
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Topaquinone
type: KeggCofactor
references: KEGG:L00003
compound type: amino acids
compound type: aromatic ring (only carbon atom)
references: CHEBI:36077
references: CHEBI:68431

RCH2NH2
type: KeggSubstrate
references: KEGG:C00375
compound type: amine group

H2O
type: KeggSubstrate
references: KEGG:C00001
compound type: H2O
references: CHEBI:15377
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Oxygen
type: KeggSubstrate
references: KEGG:C00007
compound type: others
references: CHEBI:15379
references: CHEBI:26689
references: CHEBI:27140
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Aldehyde
type: KeggProduct
references: KEGG:C00071
compound type: carbohydrate

NH3
type: KeggProduct
references: KEGG:C00014
compound type: amine group
compound type: organic ion
references: CHEBI:16134
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

H2O2
type: KeggProduct
references: KEGG:C00027
compound type: others
references: CHEBI:16240
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Substrate Schiff-base (Iminoquinone=substrate)
type: KeggIntermediate
references: KEGG:I00021

Product Schiff-base (Aminoquinol=product)
type: KeggIntermediate
references: KEGG:I00022

Aminoquinol/Semiquinone
type: KeggIntermediate
references: KEGG:I00023

Iminoquinone
type: KeggIntermediate
references: KEGG:I00024

1ksiA03
type: Pdb
references: 1ksi
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ksi
catalytic residue: TYR 286;ASP 300
cofactor binding residue: HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese)
modified residue: TPQ 387

1ksiB03
type: Pdb
references: 1ksi
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ksi
catalytic residue: TYR 286;ASP 300
cofactor binding residue: HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese)
modified residue: TPQ 387

1w2zA03
type: Pdb
references: 1w2z
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1w2z
catalytic residue: TYR 286;ASP 300
cofactor binding residue: HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese)
modified residue: TPQ 387

1w2zB03
type: Pdb
references: 1w2z
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1w2z
catalytic residue: TYR 286;ASP 300
cofactor binding residue: HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese)
modified residue: TPQ 387

1w2zC03
type: Pdb
references: 1w2z
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1w2z
catalytic residue: TYR 286;ASP 300
cofactor binding residue: HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese)
modified residue: TPQ 387

1w2zD03
type: Pdb
references: 1w2z
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1w2z
catalytic residue: TYR 286;ASP 300
cofactor binding residue: HIS 442;HIS 444;HIS 603(Copper);ASP 451;PHE 452;ASP 453;ASP 592;ILE 593(Manganese)
modified residue: TPQ 387

Stereochemical trends in copper amine oxidase reactions.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/2016294
journal: J Biol Chem
volume: 266
pages: 6795-800
published year: 1991
authors:
  item: Coleman AA
  item: Scaman CH
  item: Kang YJ
  item: Palcic MM

A Cu(I)-semiquinone state in substrate-reduced amine oxidases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/1846226
journal: Nature
volume: 349
pages: 262-4
published year: 1991
authors:
  item: Dooley DM
  item: McGuirl MA
  item: Brown DE
  item: Turowski PN
  item: McIntire WS
  item: Knowles PF

A substrate-cofactor free radical intermediate in the reaction mechanism of copper amine oxidase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/1310034
journal: Biochemistry
volume: 31
pages: 8-12
published year: 1992
authors:
  item: Pedersen JZ
  item: el-Sherbini S
  item: Finazzi-Agro A
  item: Rotilio G

Purification and characterization of pea seedling amine oxidase for crystallization studies.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/7824646
journal: Plant Physiol
volume: 106
pages: 1205-11
published year: 1994
authors:
  item: McGuirl MA
  item: McCahon CD
  item: McKeown KA
  item: Dooley DM

The reaction mechanism of copper amine oxidase: detection of intermediates by the use of substrates and inhibitors.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8845363
journal: Biochemistry
volume: 34
pages: 16375-81
published year: 1995
authors:
  item: Medda R
  item: Padiglia A
  item: Pedersen JZ
  item: Rotilio G
  item: Finazzi Agro A
  item: Floris G

Crystal structure of a eukaryotic (pea seedling) copper-containing amine oxidase at 2.2 A resolution.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS)
medline id: 96398683
references: http://www.ncbi.nlm.nih.gov/pubmed/8805580
journal: Structure
volume: 4
pages: 943-55
published year: 1996
authors:
  item: Kumar V
  item: Dooley DM
  item: Freeman HC
  item: Guss JM
  item: Harvey I
  item: McGuirl MA
  item: Wilce MC
  item: Zubak VM
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: Q43077

Visualization of dioxygen bound to copper during enzyme catalysis.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS)
medline id: 20045000
references: http://www.ncbi.nlm.nih.gov/pubmed/10576737
journal: Science
volume: 286
pages: 1724-8
published year: 1999
authors:
  item: Wilmot CM
  item: Hajdu J
  item: McPherson MJ
  item: Knowles PF
  item: Phillips SE
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P46883

Molecular mode of interaction of plant amine oxidase with the mechanism-based inhibitor 2-butyne-1,4-diamine.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10691980
journal: Eur J Biochem
volume: 267
pages: 1423-33
published year: 2000
authors:
  item: Frebort I
  item: Sebela M
  item: Svendsen I
  item: Hirota S
  item: Endo M
  item: Yamauchi O
  item: Bellelli A
  item: Lemr K
  item: Pec P

Agmatine oxidation by copper amine oxidase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11846789
journal: Eur J Biochem
volume: 269
pages: 884-92
published year: 2002
authors:
  item: Ascenzi P
  item: Fasano M
  item: Marino M
  item: Venturini G
  item: Federico R

Towards the development of selective amine oxidase inhibitors. Mechanism-based inhibition of six copper containing amine oxidases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12153561
journal: Eur J Biochem
volume: 269
pages: 3645-58
published year: 2002
authors:
  item: Shepard EM
  item: Smith J
  item: Elmore BO
  item: Kuchar JA
  item: Sayre LM
  item: Dooley DM

Differential inhibition of six copper amine oxidases by a family of 4-(aryloxy)-2-butynamines: evidence for a new mode of inactivation.
type: BibliographicResource
comment: X-ray crystallography
references: http://www.ncbi.nlm.nih.gov/pubmed/15323556
journal: Biochemistry
volume: 43
pages: 10965-78
published year: 2004
authors:
  item: O'Connell KM
  item: Langley DB
  item: Shepard EM
  item: Duff AP
  item: Jeon HB
  item: Sun G
  item: Freeman HC
  item: Guss JM
  item: Sayre LM
  item: Dooley DM
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

A theoretical study of the mechanism for the biogenesis of cofactor topaquinone in copper amine oxidases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/15038754
journal: J Am Chem Soc
volume: 126
pages: 3996-4006
published year: 2004
authors:
  item: Prabhakar R
  item: Siegbahn PE

Using xenon as a probe for dioxygen-binding sites in copper amine oxidases.
type: BibliographicResource
comment: X-ray crystallography
references: http://www.ncbi.nlm.nih.gov/pubmed/15533431
journal: J Mol Biol
volume: 344
pages: 599-607
published year: 2004
authors:
  item: Duff AP
  item: Trambaiolo DM
  item: Cohen AE
  item: Ellis PJ
  item: Juda GA
  item: Shepard EM
  item: Langley DB
  item: Dooley DM
  item: Freeman HC
  item: Guss JM
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

ReferenceForCatalyticMechanism
reference index: 1
reference section: Scheme 1

ReferenceForCatalyticMechanism
reference index: 2
reference section: Fig.3, p.263

ReferenceForCatalyticMechanism
reference index: 5
reference section: Scheme 1, p.16375-16376

ReferenceForCatalyticMechanism
reference index: 6
reference section: Fig.1, p.943-948

ReferenceForCatalyticMechanism
reference index: 7
reference section: Fig.2, p.1725-1728

ReferenceForCatalyticMechanism
reference index: 8
reference section: Fig.7, p.1431-1432

ReferenceForCatalyticMechanism
reference index: 10
reference section: Scheme 1, p.3652-3655

ReferenceForCatalyticMechanism
reference index: 11
reference section: Scheme 1, Scheme 2, p.10965-10967, p.10972-10976

ReferenceForCatalyticMechanism
reference index: 12
reference section: Fig.2, Fig.5, p.4000-4006

ReferenceForCatalyticMechanism
reference index: 13
reference section: p.599-602