EzCatDB: T00251
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DB codeT00251
CATH domainDomain 13.10.450.40 : Nuclear Transport Factor 2; Chain
Domain 23.10.450.40 : Nuclear Transport Factor 2; Chain
Domain 32.70.98.20 : 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,M00202,T00206,T00250
3.10.450.40 : Nuclear Transport Factor 2; ChainM00103,M00202,T00206,T00250

Enzyme Name
UniProtKBKEGG

Q29437
Protein namePrimary amine oxidase, liver isozymeprimary-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
Amine oxidase [copper-containing]
Serum amine oxidase
SAO
RefSeqNP_001124236.1 (Protein)
NM_001130764.1 (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 NumberQ29437
Entry nameAOCX_BOVIN
ActivityRCH(2)NH(2) + H(2)O + O(2) = RCHO + NH(3) + H(2)O(2).
Subunit
Subcellular locationSecreted, extracellular space.
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





                      
1tu5A01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1tu5B01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1tu5A02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1tu5B02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1tu5A03Bound:_CUBound:2x_CABound:TPQ 470Unbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1tu5B03Bound:_CUBound:2x_CABound:TPQ 470Unbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;Q43077, P12807, P46881
pdbCatalytic residuesCofactor-binding residuesModified residuescomment
            
1tu5A01 
 
 
 
1tu5B01 
 
 
 
1tu5A02 
 
 
 
1tu5B02 
 
 
 
1tu5A03TYR 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
1tu5B03TYR 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
ReferencesSectionsNo. 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]
PubMed ID2688201
JournalTrends Biochem Sci
Year1989
Volume14
Pages368-73
AuthorsKlinman JP
TitleQuantum mechanical effects in enzyme-catalysed hydrogen transfer reactions.
[2]
PubMed ID1846226
JournalNature
Year1991
Volume349
Pages262-4
AuthorsDooley DM, McGuirl MA, Brown DE, Turowski PN, McIntire WS, Knowles PF
TitleA Cu(I)-semiquinone state in substrate-reduced amine oxidases.
[3]
PubMed ID7791619
JournalMethods Enzymol
Year1995
Volume249
Pages373-97
AuthorsBahnson BJ, Klinman JP
TitleHydrogen tunneling in enzyme catalysis.
[4]
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
[5]
PubMed ID12153561
JournalEur J Biochem
Year2002
Volume269
Pages3645-58
AuthorsShepard EM, Smith J, Elmore BO, Kuchar JA, Sayre LM, Dooley DM
TitleTowards the development of selective amine oxidase inhibitors. Mechanism-based inhibition of six copper containing amine oxidases.
[6]
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
[7]
PubMed ID15701511
JournalJ Mol Biol
Year2005
Volume346
Pages991-1004
AuthorsLunelli M, Di Paolo ML, Biadene M, Calderone V, Battistutta R, Scarpa M, Rigo A, Zanotti G
TitleCrystal structure of amine oxidase from bovine serum.
Related PDB1tu5

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):

createdupdated
2005-05-262009-02-26


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