Multicopper oxidase explained

Symbol:	Cu-oxidase
Multicopper oxidase (type 1)
Pfam:	PF00394
Pfam Clan:	CL0026
Interpro:	IPR001117
Prosite:	PDOC00076
Scop:	1aoz
Membranome Superfamily:	253

Symbol:	Cu-oxidase_2
Multicopper oxidase (type 2)
Pfam:	PF07731
Pfam Clan:	CL0026
Interpro:	IPR011706
Scop:	1aoz

Symbol:	Cu-oxidase_3
Multicopper oxidase (type 3)
Pfam:	PF07732
Pfam Clan:	CL0026
Interpro:	IPR011707
Scop:	1aoz

Symbol:	Cu-oxidase_4
CMulti-copper polyphenol oxidoreductase laccase
Pfam:	PF02578
Interpro:	IPR003730

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]

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 (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 (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, a 3-domain enzyme found in higher plants.
• Nitrite reductase, 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.

References

^[10]

Notes and References

1. Bento I, Martins LO, Gato Lopes G, Arménia Carrondo M, Lindley PF . Dioxygen reduction by multi-copper oxidases; a structural perspective . . 21 . 3507–13 . November 2005 . 16234932 . 10.1039/b504806k .
2. Messerschmidt A, Huber R . The blue oxidases, ascorbate oxidase, laccase and ceruloplasmin. Modelling and structural relationships . Eur. J. Biochem. . 187 . 2 . 341–52 . January 1990 . 2404764 . 10.1111/j.1432-1033.1990.tb15311.x . free .
3. Ouzounis C, Sander C . A structure-derived sequence pattern for the detection of type I copper binding domains in distantly related proteins . FEBS Lett. . 279 . 1 . 73–8 . February 1991 . 1995346 . 10.1016/0014-5793(91)80254-Z. 10299194 .
4. Roberts SA, Weichsel A, Grass G, Thakali K, Hazzard JT, Tollin G, Rensing C, Montfort WR . Crystal structure and electron transfer kinetics of CueO, a multicopper oxidase required for copper homeostasis in Escherichia coli . Proc. Natl. Acad. Sci. U.S.A. . 99 . 5 . 2766–71 . March 2002 . 11867755 . 122422 . 10.1073/pnas.052710499 . free .
5. Mano . Nicolas . de Poulpiquet . Anne . 2018-03-14 . O 2 Reduction in Enzymatic Biofuel Cells . Chemical Reviews . en . 118 . 5 . 2392–2468 . 10.1021/acs.chemrev.7b00220 . 0009-2665.
6. Nakamura K, Kawabata T, Yura K, Go N . Novel types of two-domain multi-copper oxidases: possible missing links in the evolution . FEBS Lett. . 553 . 3 . 239–44 . October 2003 . 14572631 . 10.1016/S0014-5793(03)01000-7. 85060706 . free .
7. Suzuki S, Kataoka K, Yamaguchi K . Metal coordination and mechanism of multicopper nitrite reductase . Acc. Chem. Res. . 33 . 10 . 728–35 . October 2000 . 11041837 . 10.1021/ar9900257.
8. Mann KG, Jenny RJ, Krishnaswamy S . Cofactor proteins in the assembly and expression of blood clotting enzyme complexes . Annu. Rev. Biochem. . 57 . 915–56 . 1988 . 3052293 . 10.1146/annurev.bi.57.070188.004411 .
9. Askwith C, Eide D, Van Ho A, Bernard PS, Li L, Davis-Kaplan S, Sipe DM, Kaplan J . The FET3 gene of S. cerevisiae encodes a multicopper oxidase required for ferrous iron uptake . Cell . 76 . 2 . 403–10 . January 1994 . 8293473 . 10.1016/0092-8674(94)90346-8. 27473253 .
10. Lawton . Thomas J. . Sayavedra-Soto . Luis A. . Arp . Daniel J. . Rosenzweig . Amy C. . 2009-04-10 . Crystal Structure of a Two-domain Multicopper Oxidase * . Journal of Biological Chemistry . English . 284 . 15 . 10174–10180 . 10.1074/jbc.M900179200 . 0021-9258 . 19224923. free . 2665071 .