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 | |||||||||
| Identifiers | |||||||||
| Symbol | Cu-oxidase | ||||||||
| Pfam | PF00394 | ||||||||
| Pfam clan | CL0026 | ||||||||
| InterPro | IPR001117 | ||||||||
| PROSITE | PDOC00076 | ||||||||
| SCOP2 | 1aoz / SCOPe / SUPFAM | ||||||||
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| 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 | ||||||||
| |||||||||
| 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 | ||||||||
| |||||||||
| 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 | ||||||||
| |||||||||
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 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.[4] 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.[5][6]
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 FET3 required for ferrous iron uptake [8]; yeast hypothetical protein YFL041w; and the fission yeast homologue SpAC1F7.08.
References
- ^ Bento I, Martins LO, Gato Lopes G, Arménia Carrondo M, Lindley PF (2005). "Dioxygen reduction by multi-copper oxidases; a structural perspective". Dalton Trans (21): 3507–13. doi:10.1039/b504806k. PMID 16234932.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Messerschmidt A, Huber R (1990). "The blue oxidases, ascorbate oxidase, laccase and ceruloplasmin. Modelling and structural relationships". Eur. J. Biochem. 187 (2): 341–52. PMID 2404764.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Ouzounis C, Sander C (1991). "A structure-derived sequence pattern for the detection of type I copper binding domains in distantly related proteins". FEBS Lett. 279 (1): 73–8. PMID 1995346.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ a b Roberts SA, Weichsel A, Grass G, Thakali K, Hazzard JT, Tollin G, Rensing C, Montfort WR (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): 2766–71. doi:10.1073/pnas.052710499. PMC 122422. PMID 11867755.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Nakamura K, Kawabata T, Yura K, Go N (2003). "Novel types of two-domain multi-copper oxidases: possible missing links in the evolution". FEBS Lett. 553 (3): 239–44. PMID 14572631.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Suzuki S, Kataoka K, Yamaguchi K (2000). "Metal coordination and mechanism of multicopper nitrite reductase". Acc. Chem. Res. 33 (10): 728–35. PMID 11041837.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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. PMID 3052293.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Askwith C, Eide D, Van Ho A, Bernard PS, Li L, Davis-Kaplan S, Sipe DM, Kaplan J (1994). "The FET3 gene of S. cerevisiae encodes a multicopper oxidase required for ferrous iron uptake". Cell. 76 (2): 403–10. PMID 8293473.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link)
This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Multicopper oxidase Provide feedback
This entry contains many divergent copper oxidase-like domains that are not recognised by the PF00394 model.
Literature references
-
Messerschmidt A, Huber R; , Eur J Biochem 1990;187:341-352.: The blue oxidases, ascorbate oxidase, laccase and ceruloplasmin. Modelling and structural relationships. PUBMED:2404764 EPMC:2404764
-
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
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Page CC, Moser CC, Chen X, Dutton PL; , Nature 1999;402:47-52.: Natural engineering principles of electron tunnelling in biological oxidation-reduction. PUBMED:10573417 EPMC:10573417
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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
| HOMSTRAD: | Cu-oxidase Cu_nir |
| SCOP: | 1aoz |
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 the N-terminal domain (or coupled binuclear) of multicopper oxidase.
Gene Ontology
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) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan CU_oxidase (CL0026), which has the following description:
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 SoxEAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
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| Seed (81) |
Full (31736) |
Representative proteomes | UniProt (85067) |
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| RP15 (3714) |
RP35 (13756) |
RP55 (27510) |
RP75 (41728) |
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| HTML | |||||||
| PP/heatmap | 1 | ||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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| Seed (81) |
Full (31736) |
Representative proteomes | UniProt (85067) |
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|---|---|---|---|---|---|---|---|
| RP15 (3714) |
RP35 (13756) |
RP55 (27510) |
RP75 (41728) |
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| Raw Stockholm | |||||||
| Gzipped | |||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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Curation and family details
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Curation
| Seed source: | PfamB-43 (Release 14.0) |
| Previous IDs: | none |
| Type: | Domain |
| Sequence Ontology: | SO:0000417 |
| Author: |
Studholme DJ 
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| Number in seed: | 81 |
| Number in full: | 31736 |
| Average length of the domain: | 112.2 aa |
| Average identity of full alignment: | 26 % |
| Average coverage of the sequence by the domain: | 20.11 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 119 | ||||||||||||
| Family (HMM) version: | 18 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Structures
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 1000 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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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.
