Summary: Multicopper oxidase
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Multicopper oxidase Edit Wikipedia article
|Multicopper oxidase (type 1)|
crystal structures of e. coli laccase cueo under different copper binding situations
|SCOPe||1aoz / SUPFAM|
|Multicopper oxidase (type 2)|
active laccase from trametes versicolor complexed with 2,5-xylidine
|SCOPe||1aoz / SUPFAM|
|Multicopper oxidase (type 3)|
crystal structures of e. coli laccase cueo under different copper binding situations
|SCOPe||1aoz / SUPFAM|
|CMulti-copper polyphenol oxidoreductase laccase|
crystal structure of protein cc_0490 from caulobacter crescentus, pfam duf152
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. 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). 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. Multicopper oxidases include:
- Ceruloplasmin EC 22.214.171.124 (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 126.96.36.199 (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.
- Ascorbate oxidase EC 188.8.131.52, a 3-domain enzyme found in higher plants.
- Nitrite reductase EC 184.108.40.206, a 2-domain enzyme containing type-1 and type-2 copper centres.
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); yeast Fet3p (FET3) required for ferrous iron uptake; yeast hypothetical protein YFL041w; and the fission yeast homologue SpAC1F7.08.
- Bento I, Martins LO, Gato Lopes G, ArmÃ©nia Carrondo M, Lindley PF (November 2005). "Dioxygen reduction by multi-copper oxidases; a structural perspective". Dalton Transactions (21): 3507â€“13. doi:10.1039/b504806k. PMID 16234932.
- Messerschmidt A, Huber R (January 1990). "The blue oxidases, ascorbate oxidase, laccase and ceruloplasmin. Modelling and structural relationships". Eur. J. Biochem. 187 (2): 341â€“52. doi:10.1111/j.1432-1033.1990.tb15311.x. PMID 2404764.
- Ouzounis C, Sander C (February 1991). "A structure-derived sequence pattern for the detection of type I copper binding domains in distantly related proteins". FEBS Lett. 279 (1): 73â€“8. doi:10.1016/0014-5793(91)80254-Z. PMID 1995346.
- Roberts SA, Weichsel A, Grass G, Thakali K, Hazzard JT, Tollin G, Rensing C, Montfort WR (March 2002). "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): 2766â€“71. doi:10.1073/pnas.052710499. PMC 122422. PMID 11867755.
- 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): 239â€“44. doi:10.1016/S0014-5793(03)01000-7. PMID 14572631.
- Suzuki S, Kataoka K, Yamaguchi K (October 2000). "Metal coordination and mechanism of multicopper nitrite reductase". Acc. Chem. Res. 33 (10): 728â€“35. doi:10.1021/ar9900257. PMID 11041837.
- Mann KG, Jenny RJ, Krishnaswamy S (1988). "Cofactor proteins in the assembly and expression of blood clotting enzyme complexes". Annu. Rev. Biochem. 57: 915â€“56. doi:10.1146/annurev.bi.57.070188.004411. PMID 3052293.
- 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): 403â€“10. doi:10.1016/0092-8674(94)90346-8. PMID 8293473.
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Multicopper oxidase Provide feedback
This entry contains many divergent copper oxidase-like domains that are not recognised by the PF00394 model.
Messerschmidt A, Ladenstein R, Huber R, Bolognesi M, Avigliano L, Petruzzelli R, Rossi A, Finazzi-Agro A; , J Mol Biol 1992;224:179-205.: Refined crystal structure of ascorbate oxidase at 1.9 A resolution. PUBMED:1548698 EPMC:1548698
Grossmann JG, Ingledew WJ, Harvey I, Strange RW, Hasnain SS; , Biochemistry 1995;34:8406-8414.: X-ray absorption studies and homology modeling define the structural features that specify the nature of the copper site in rusticyanin. PUBMED:7599131 EPMC:7599131
Internal database links
|SCOOP:||Copper-bind Cu-oxidase Cu-oxidase_2 Cupredoxin_1|
|Similarity to PfamA using HHSearch:||Cu-oxidase_2|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR011707
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.
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 [PUBMED:16234932]. 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) [PUBMED:2404764, PUBMED:1995346]. 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 [PUBMED:11867755]. Multicopper oxidases include:
- Ceruloplasmin (EC) (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) (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 [PUBMED:11867755].
- Ascorbate oxidase (EC), a 3-domain enzyme found in higher plants.
- Nitrite reductase (EC), a 2-domain enzyme containing type-1 and type-2 copper centres [PUBMED:14572631, PUBMED:11041837].
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) [PUBMED:3052293]; yeast FET3 required for ferrous iron uptake [PUBMED:8293473]; yeast hypothetical protein YFL041w; and the fission yeast homologue SpAC1F7.08.
This entry represents multicopper oxidase type 3 (or coupled binuclear) domains.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||copper ion binding (GO:0005507)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Many of the proteins in this family contain multiple similar copies of this plastocyanin-like domain.
The clan contains the following 15 members:Copper-bind COX2 COX_ARM Cu-oxidase Cu-oxidase_2 Cu-oxidase_3 Cu_bind_like Cupredoxin_1 CzcE DP-EP Ephrin hGDE_N PAD_N PixA SoxE
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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|Seed source:||PfamB-43 (Release 14.0)|
|Number in seed:||85|
|Number in full:||20608|
|Average length of the domain:||112.00 aa|
|Average identity of full alignment:||28 %|
|Average coverage of the sequence by the domain:||20.47 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||15|
|Download:||download the raw HMM for this family|
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There are 9 interactions for this family. More...
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Cu-oxidase_3 domain has been found. There are 738 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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