Multicopper oxidase

In molecular biology, multicopper oxidases are enzymes which oxidise their substrate by accepting electrons at a mononuclear copper centre and transferring them to a trinuclear copper centre; dioxygen binds to the trinuclear centre and, following the transfer of four electrons, is reduced to two molecules of water.^[1] There are three spectroscopically different copper centres found in multicopper oxidases: type 1 (or blue), type 2 (or normal) and type 3 (or coupled binuclear).^[2][3] Multicopper oxidases consist of 2, 3 or 6 of these homologous domains, which also share homology with the cupredoxins azurin and plastocyanin. Structurally, these domains consist of a cupredoxin-like fold, a beta-sandwich consisting of 7 strands in 2 beta-sheets, arranged in a Greek-key beta-barrel.^[4]

Multicopper oxidase (type 1)
crystal structures of e. coli laccase cueo under different copper binding situations
Identifiers
Symbol	Cu-oxidase
Pfam	PF00394
Pfam clan	CL0026
InterPro	IPR001117
PROSITE	PDOC00076
SCOP2	1aoz / SCOPe / SUPFAM
Membranome	253
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Multicopper oxidase (type 2)
active laccase from trametes versicolor complexed with 2,5-xylidine
Identifiers
Symbol	Cu-oxidase_2
Pfam	PF07731
Pfam clan	CL0026
InterPro	IPR011706
SCOP2	1aoz / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Multicopper oxidase (type 3)
crystal structures of e. coli laccase cueo under different copper binding situations
Identifiers
Symbol	Cu-oxidase_3
Pfam	PF07732
Pfam clan	CL0026
InterPro	IPR011707
SCOP2	1aoz / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

CMulti-copper polyphenol oxidoreductase laccase
crystal structure of protein cc_0490 from caulobacter crescentus, pfam duf152
Identifiers
Symbol	Cu-oxidase_4
Pfam	PF02578
InterPro	IPR003730
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

The family of multicopper oxidases can be divided into three groups based on the electron-donating substrate. ^[5] Laccases oxidize a variety of organic substrates, metalloxidases accept metal substrates and a third group contains multicopper oxidases that are specific towards one single substrate. Multicopper oxidases include:

• Ceruloplasmin EC 1.16.3.1 (ferroxidase), a 6-domain enzyme found in the serum of mammals and birds that oxidizes different inorganic and organic substances; exhibits internal sequence homology that appears to have evolved from the triplication of a Cu-binding domain similar to that of laccase and ascorbate oxidase.
• Laccase EC 1.10.3.2 (urishiol oxidase), a 3-domain enzyme found in fungi and plants, which oxidizes different phenols and diamines. CueO is a laccase found in Escherichia coli that is involved in copper-resistance.^[4]
• Ascorbate oxidase EC 1.10.3.3, a 3-domain enzyme found in higher plants.
• Nitrite reductase EC 1.7.2.1, a 2-domain enzyme containing type-1 and type-2 copper centres.^[6][7]

In addition to the above enzymes there are a number of other proteins that are similar to the multi-copper oxidases in terms of structure and sequence, some of which have lost the ability to bind copper. These include: copper resistance protein A (copA) from a plasmid in Pseudomonas syringae; domain A of (non-copper binding) blood coagulation factors V (Fa V) and VIII (Fa VIII);^[8] yeast Fet3p (FET3) required for ferrous iron uptake;^[9] yeast hypothetical protein YFL041w; and the fission yeast homologue SpAC1F7.08.