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; dioxygenbinds 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 oxidases include:
CeruloplasminEC1.16.3.1 (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.
LaccaseEC1.10.3.2 (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 oxidaseEC1.10.3.3, a 3-domain enzyme found in higher plants.
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);[7]yeast Fet3p (FET3) required for ferrousiron uptake;[8]yeast hypothetical protein YFL041w; and the fission yeasthomologue SpAC1F7.08.
References[]
^Bento I, Martins LO, Gato Lopes G, Arménia Carrondo M, Lindley PF (November 2005). "Dioxygen reduction by multi-copper oxidases; a structural perspective". Dalton Transactions (21): 3507–13. doi:10.1039/b504806k. PMID16234932.
^Nakamura K, Kawabata T, Yura K, Go N (October 2003). "Novel types of two-domain multi-copper oxidases: possible missing links in the evolution". FEBS Lett. 553 (3): 239–44. doi:10.1016/S0014-5793(03)01000-7. PMID14572631. S2CID85060706.
^Suzuki S, Kataoka K, Yamaguchi K (October 2000). "Metal coordination and mechanism of multicopper nitrite reductase". Acc. Chem. Res. 33 (10): 728–35. doi:10.1021/ar9900257. PMID11041837.
^Mann KG, Jenny RJ, Krishnaswamy S (1988). "Cofactor proteins in the assembly and expression of blood clotting enzyme complexes". Annu. Rev. Biochem. 57: 915–56. doi:10.1146/annurev.bi.57.070188.004411. PMID3052293.
^Askwith C, Eide D, Van Ho A, Bernard PS, Li L, Davis-Kaplan S, Sipe DM, Kaplan J (January 1994). "The FET3 gene of S. cerevisiae encodes a multicopper oxidase required for ferrous iron uptake". Cell. 76 (2): 403–10. doi:10.1016/0092-8674(94)90346-8. PMID8293473. S2CID27473253.