<p>Copper is one of the most prevalent transition metals in living organisms and its biological function is intimately related to its redox properties. Since free copper is toxic, even at very low concentrations, its homeostasis in living organisms is tightly controlled by subtle molecular mechanisms. In eukaryotes, before being transported inside the cell via the high-affinity copper transporters of the CTR family, the copper (II) ion is reduced to copper (I). In blue copper proteins such as cupredoxin, the copper (I) ion form is stabilised by a constrained His2Cys coordination environment.</p><p>Multicopper oxidases 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 [<cite idref="PUB00035913"/>]. 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) [<cite idref="PUB00001382"/>, <cite idref="PUB00001602"/>]. Multicopper oxidases consist of 2, 3 or 6 of these homologous domains, which also share homology to 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 [<cite idref="PUB00011817"/>]. Multicopper oxidases include:</p><p> <ul><li>Ceruloplasmin (<db_xref db="EC" dbkey="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. </li><li>Laccase (<db_xref db="EC" dbkey="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 <taxon tax_id="562">Escherichia coli</taxon> that is involved in copper-resistance [<cite idref="PUB00011817"/>].</li><li>Ascorbate oxidase (<db_xref db="EC" dbkey="1.10.3.3"/>), a 3-domain enzyme found in higher plants.</li><li>Nitrite reductase (<db_xref db="EC" dbkey="1.7.2.1"/>), a 2-domain enzyme containing type-1 and type-2 copper centres [<cite idref="PUB00035911"/>, <cite idref="PUB00035912"/>].</li></ul> </p><p>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 <taxon tax_id="317">Pseudomonas syringae</taxon>; domain A of (non-copper binding) blood coagulation factors V (Fa V) and VIII (Fa VIII) [<cite idref="PUB00000062"/>]; yeast FET3 required for ferrous iron uptake [<cite idref="PUB00000901"/>]; yeast hypothetical protein YFL041w; and the fission yeast homologue SpAC1F7.08.</p><p> This entry represents multicopper oxidase type 3 (or coupled binuclear) domains. </p> Multicopper oxidase, type 3