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325  structures 2516  species 4  interactions 9871  sequences 57  architectures

Family: Cu-oxidase (PF00394)

Summary: Multicopper oxidase

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This is the Wikipedia entry entitled "Multicopper oxidase". More...

Multicopper oxidase Edit Wikipedia article

Multicopper oxidase (type 1)
PDB 2fqg EBI.jpg
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
SCOP 1aoz
SUPERFAMILY 1aoz
Multicopper oxidase (type 2)
PDB 1kya EBI.jpg
active laccase from trametes versicolor complexed with 2,5-xylidine
Identifiers
Symbol Cu-oxidase_2
Pfam PF07731
Pfam clan CL0026
InterPro IPR011706
SCOP 1aoz
SUPERFAMILY 1aoz
Multicopper oxidase (type 3)
PDB 2fqe EBI.jpg
crystal structures of e. coli laccase cueo under different copper binding situations
Identifiers
Symbol Cu-oxidase_3
Pfam PF07732
Pfam clan CL0026
InterPro IPR011707
SCOP 1aoz
SUPERFAMILY 1aoz
CMulti-copper polyphenol oxidoreductase laccase
PDB 1xfj EBI.jpg
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:

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 ferrous iron uptake;[8] yeast hypothetical protein YFL041w; and the fission yeast homologue SpAC1F7.08.

References

  1. ^ 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. PMID 16234932. 
  2. ^ Messerschmidt A, Huber R (January 1990). "The blue oxidases, ascorbate oxidase, laccase and ceruloplasmin. Modelling and structural relationships". Eur. J. Biochem. 187 (2): 341–52. doi:10.1111/j.1432-1033.1990.tb15311.x. PMID 2404764. 
  3. ^ 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): 73–8. doi:10.1016/0014-5793(91)80254-Z. PMID 1995346. 
  4. ^ a b 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): 2766–71. doi:10.1073/pnas.052710499. PMC 122422. PMID 11867755. 
  5. ^ 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. PMID 14572631. 
  6. ^ 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. PMID 11041837. 
  7. ^ 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. 
  8. ^ 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. PMID 8293473. 

This article incorporates text from the public domain Pfam and InterPro IPR001117

This article incorporates text from the public domain Pfam and InterPro IPR011706

This article incorporates text from the public domain Pfam and InterPro IPR011707

This article incorporates text from the public domain Pfam and InterPro IPR003730

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

Many of the proteins in this family contain multiple similar copies of this plastocyanin-like domain.

Literature references

  1. 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

  2. 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


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001117

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 1 (blue) domains. These domains are also present in proteins that have lost the ability to bind copper.

Gene Ontology

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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 9 members:

Copper-bind COX2 Cu-oxidase Cu-oxidase_2 Cu-oxidase_3 Cu_bind_like Cupredoxin_1 Ephrin SoxE

Alignments

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  Seed
(72)
Full
(9871)
Representative proteomes NCBI
(9906)
Meta
(260)
RP15
(504)
RP35
(1249)
RP55
(1757)
RP75
(2092)
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  Seed
(72)
Full
(9871)
Representative proteomes NCBI
(9906)
Meta
(260)
RP15
(504)
RP35
(1249)
RP55
(1757)
RP75
(2092)
Alignment:
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  Seed
(72)
Full
(9871)
Representative proteomes NCBI
(9906)
Meta
(260)
RP15
(504)
RP35
(1249)
RP55
(1757)
RP75
(2092)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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Trees

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

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

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Seed source: Prosite
Previous IDs: none
Type: Domain
Author: Finn RD, Griffiths-Jones SR
Number in seed: 72
Number in full: 9871
Average length of the domain: 140.70 aa
Average identity of full alignment: 23 %
Average coverage of the sequence by the domain: 37.09 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.3 19.9
Trusted cut-off 20.3 19.9
Noise cut-off 20.2 19.8
Model length: 159
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 4 interactions for this family. More...

Cu-oxidase Cu-oxidase_3 Cu-oxidase_2 Copper-bind

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 domain has been found. There are 325 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 seqence.

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