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InterPro: IPR015801 Copper amine oxidase, N2/N3-terminal
Protein matches
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UniProtKB Matches: 437 proteins |
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Accession
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IPR015801 Cu_amine_oxidase_N2/3 |
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Secondary
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IPR000269
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Type
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Domain |
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Signatures
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InterPro Relationships
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Found in
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IPR000269 Copper amine oxidase
IPR016182 Copper amine oxidase, N-terminal
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Contains
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IPR015800 Copper amine oxidase, N2-terminal
IPR015802 Copper amine oxidase, N3-terminal
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GO Term annotation
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Process
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GO:0009308 amine metabolic process
GO:0055114 oxidation reduction
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Function
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GO:0005507 copper ion binding
GO:0008131 amine oxidase activity
GO:0048038 quinone binding
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InterPro annotation
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 Entry Details in BioMart
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Abstract
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Amine oxidases (AO) are enzymes that catalyse the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. There are two classes of amine oxidases: flavin-containing (EC:1.4.3.4) and copper-containing (EC:1.4.3.6). Copper-containing AO act as a disulphide-linked homodimer. They catalyse the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone as cofactor [1]:
RCH2NH2 + H2O + O2 = RCHO + NH3 + H2O2
Copper-containing amine oxidases are found in bacteria, fungi, plants and animals. In prokaryotes, the enzyme enables various amine substrates to be used as sources of carbon and nitrogen [2, 3]. In eukaryotes they have a broader range of functions, including cell differentiation and growth, wound healing, detoxification and cell signalling [4].
The copper amine oxidases occur as mushroom-shaped homodimers of 70-95 kDa, each monomer containing a copper ion and a covalently bound redox cofactor, topaquinone (TPQ). TPQ is formed by post-translational modification of a conserved tyrosine residue. The copper ion is coordinated with three histidine residues and two water molecules in a distorted square pyramidal geometry, and has a dual function in catalysis and TPQ biogenesis. The catalytic domain is the largest of the 3-4 domains found in copper amine oxidases, and consists of a beta sandwich of 18 strands in two sheets. The active site is buried and requires a conformational change to allow the substrate access. The two N-terminal domains share a common structural fold, its core consisting of a five-stranded antiparallel beta sheet twisted around an alpha helix. The D1 domains from the two subunits comprise the stalk, of the mushroom-shaped dimer, and interact with each other but do not pack tightly against each other [1, 5].
This entry represents the two N-terminal domains (N2/N3) that share a similar structure.
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Structural links
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Database links
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Publications
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1.
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Parsons MR, Convery MA, Wilmot CM, Yadav KD, Blakeley V, Corner AS, Phillips SE, McPherson MJ, Knowles PF.
Crystal structure of a quinoenzyme: copper amine oxidase of Escherichia coli at 2 A resolution.
Structure 3 1171-84 1995
[PubMed: 8591028]
http://dx.doi.org/10.1016/S0969-2126(01)00253-2
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2.
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Wilmot CM, Murray JM, Alton G, Parsons MR, Convery MA, Blakeley V, Corner AS, Palcic MM, Knowles PF, McPherson MJ, Phillips SE.
Catalytic mechanism of the quinoenzyme amine oxidase from Escherichia coli: exploring the reductive half-reaction.
Biochemistry 36 1608-20 1997
[PubMed: 9048544]
http://dx.doi.org/10.1021/bi962205j
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3.
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Wilce MC, Dooley DM, Freeman HC, Guss JM, Matsunami H, McIntire WS, Ruggiero CE, Tanizawa K, Yamaguchi H.
Crystal structures of the copper-containing amine oxidase from Arthrobacter globiformis in the holo and apo forms: implications for the biogenesis of topaquinone.
Biochemistry 36 16116-33 1997
[PubMed: 9405045]
http://dx.doi.org/10.1021/bi971797i
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4.
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Kumar V, Dooley DM, Freeman HC, Guss JM, Harvey I, McGuirl MA, Wilce MC, Zubak VM.
Crystal structure of a eukaryotic (pea seedling) copper-containing amine oxidase at 2.2 A resolution.
Structure 4 943-55 1996
[PubMed: 8805580]
http://dx.doi.org/10.1016/S0969-2126(96)00101-3
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5.
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Wilmot CM, Hajdu J, McPherson MJ, Knowles PF, Phillips SE.
Visualization of dioxygen bound to copper during enzyme catalysis.
Science 286 1724-8 1999
[PubMed: 10576737]
http://dx.doi.org/10.1126/science.286.5445.1724
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Additional Reading
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Taki M, Murakawa T, Nakamoto T, Uchida M, Hayashi H, Tanizawa K, Yamamoto Y, Okajima T.
Further insight into the mechanism of stereoselective proton abstraction by bacterial copper amine oxidase.
Biochemistry 47 2008 7726-33
[PubMed: 18627131]
http://dx.doi.org/10.1021/bi800623f
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Langley DB, Trambaiolo DM, Duff AP, Dooley DM, Freeman HC, Guss JM.
Complexes of the copper-containing amine oxidase from Arthrobacter globiformis with the inhibitors benzylhydrazine and tranylcypromine.
Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 64 2008 577-83
[PubMed: 18607080]
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Langley DB, Brown DE, Cheruzel LE, Contakes SM, Duff AP, Hilmer KM, Dooley DM, Gray HB, Guss JM, Freeman HC.
Enantiomer-specific binding of ruthenium(II) molecular wires by the amine oxidase of Arthrobacter globiformis.
J. Am. Chem. Soc. 130 2008 8069-78
[PubMed: 18507382]
http://dx.doi.org/10.1021/ja801289f
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Johnson BJ, Cohen J, Welford RW, Pearson AR, Schulten K, Klinman JP, Wilmot CM.
Exploring molecular oxygen pathways in Hansenula polymorpha copper-containing amine oxidase.
J. Biol. Chem. 282 2007 17767-76
[PubMed: 17409383]
http://dx.doi.org/10.1074/jbc.M701308200
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Holt A, Smith DJ, Cendron L, Zanotti G, Rigo A, Di Paolo ML.
Multiple binding sites for substrates and modulators of semicarbazide-sensitive amine oxidases: kinetic consequences.
Mol. Pharmacol. 73 2008 525-38
[PubMed: 17989349]
http://dx.doi.org/10.1124/mol.107.040964
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