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314  structures 421  species 2  interactions 2338  sequences 150  architectures

Family: An_peroxidase (PF03098)

Summary: Animal haem peroxidase

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This is the Wikipedia entry entitled "Animal heme-dependent peroxidases". More...

Animal heme-dependent peroxidases Edit Wikipedia article

Animal heme-dependent peroxidase
Idnu.png
Crystal structure of the human myeloperoxidase-thiocyanate complex.[1]
Identifiers
Symbol An_peroxidase
Pfam PF03098
InterPro IPR002007
PROSITE PDOC00394
SCOP 1mhl
SUPERFAMILY 1mhl
OPM superfamily 37
OPM protein 1q4g
CDD cd05396

Animal heme-dependent peroxidases is a family of peroxidases.

Peroxidases are found in bacteria, fungi, plants and animals. On the basis of sequence similarity, a number of animal heme peroxidases can be categorized as members of a superfamily: myeloperoxidase (MPO); eosinophil peroxidase (EPO); lactoperoxidase (LPO); thyroid peroxidase (TPO); prostaglandin H synthase (PGHS); and peroxidasin.[2][3][4]

Function[edit]

Myeloperoxidase (MPO) plays a major role in the oxygen-dependent microbicidal system of neutrophils. EPO from eosinophilic granulocytes participates in immunological reactions, and potentiates tumor necrosis factor (TNF) production and hydrogen peroxide release by human monocyte-derived macrophages.[5][6] MPO (and possibly EPO) primarily use Cl-ions and H2O2 to form hypochlorous acid (HOCl), which can effectively kill bacteria or parasites. In secreted fluids, LPO catalyses the oxidation of thiocyanate ions (SCN-) by H2O2, producing the weak oxidizing agent hypothiocyanite (OSCN-), which has bacteriostatic activity.[7] TPO uses I- ions and H2O2 to generate iodine, and plays a central role in the biosynthesis of thyroid hormones T3 and T4. Myeloperoxidase (PDB 1dnu), for example, resides in the human nucleus and lysosome and acts as a defense response to oxidative stress, preventing apoptosis of the cell.[1]

Structure[edit]

3D structures of MPO and PGHS have been reported. MPO is a homodimer: each monomer consists of a light (A or B) and a heavy (C or D) chain resulting from post-translational excision of 6 residues from the common precursor. Monomers are linked by a single inter-chain disulfide. Each monomer includes a bound calcium ion.[8] PGHS exists as a symmetric dimer, each monomer of which consists of 3 domains: an N-terminal epidermal growth factor (EGF) like module; a membrane-binding domain; and a large C-terminal catalytic domain containing the cyclooxygenase and the peroxidase active sites. The catalytic domain shows striking structural similarity to MPO. The image at the top of this page is an example of Myeloperoxidase 1dnu derived from X-ray diffraction with resolution 1.85 angstrom.[1]

Active site[edit]

The cyclooxygenase active site, which catalyzes the formation of prostaglandin G2 (PGG2) from arachidonic acid, resides at the apex of a long hydrophobic channel, extending from the membrane-binding domain to the center of the molecule. The peroxidase active site, which catalyzes the reduction of PGG2 to PGH2, is located on the other side of the molecule, at the heme binding site.[9] Both MPO and the catalytic domain of PGHS are mainly alpha-helical, 19 helices being identified as topologically and spatially equivalent; PGHS contains 5 additional N-terminal helices that have no equivalent in MPO. In both proteins, three Asn residues in each monomer are glycosylated.

Human proteins containing this domain[edit]

The following is a list of human proteins containing this domain:[10]

DUOX1; DUOX2; EPX; LPO; MPO; PTGS1; PTGS2; PXDNL; TPO

References[edit]

  1. ^ a b c PDB 1dnu; Blair-Johnson M, Fiedler T, Fenna R (November 2001). "Human myeloperoxidase: structure of a cyanide complex and its interaction with bromide and thiocyanate substrates at 1.9 A resolution". Biochemistry 40 (46): 13990–7. doi:10.1021/bi0111808. PMID 11705390. 
  2. ^ Nelson RE, Fessler LI, Takagi Y, Blumberg B, Keene DR, Olson PF, Parker CG, Fessler JH (1994). "Peroxidasin: a novel enzyme-matrix protein of Drosophila development". EMBO J. 13 (15): 3438–3447. PMC 395246. PMID 8062820. 
  3. ^ Poulos TL, Li H (1994). "Structural variation in heme enzymes: a comparative analysis of peroxidase and P450 crystal structures". Structure 2 (6): 461–464. doi:10.1016/S0969-2126(00)00046-0. PMID 7922023. 
  4. ^ Kimura S, Ikeda-Saito M (1988). "Human myeloperoxidase and thyroid peroxidase, two enzymes with separate and distinct physiological functions, are evolutionarily related members of the same gene family". Proteins 3 (2): 113–120. doi:10.1002/prot.340030206. PMID 2840655. 
  5. ^ Kimura S, Hong YS, Kotani T, Ohtaki S, Kikkawa F (1989). "Structure of the human thyroid peroxidase gene: comparison and relationship to the human myeloperoxidase gene". Biochemistry 28 (10): 4481–4489. doi:10.1021/bi00436a054. PMID 2548579. 
  6. ^ Spessotto P, Dri P, Bulla R, Zabucchi G, Patriarca P (1995). "Human eosinophil peroxidase enhances tumor necrosis factor and hydrogen peroxide release by human monocyte-derived macrophages". Eur. J. Immunol. 25 (5): 1366–1373. doi:10.1002/eji.1830250535. PMID 7774640. 
  7. ^ Wever R, Kast WM, Kasinoedin JH, Boelens R (1982). "The peroxidation of thiocyanate catalysed by myeloperoxidase and lactoperoxidase". Biochim. Biophys. Acta 709 (2): 212–219. doi:10.1016/0167-4838(82)90463-0. PMID 6295491. 
  8. ^ Fenna RE, Zeng J (1992). "X-ray crystal structure of canine myeloperoxidase at 3 A resolution". J. Mol. Biol. 226 (1): 185–207. doi:10.1016/0022-2836(92)90133-5. PMID 1320128. 
  9. ^ Picot D, Loll PJ, Garavito RM (1994). "The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1". Nature 367 (6460): 243–249. doi:10.1038/367243a0. PMID 8121489. 
  10. ^ Zamocky M, Jakopitsch C, Furtmüller PG, Dunand C, Obinger C (August 2008). "The peroxidase-cyclooxygenase superfamily: Reconstructed evolution of critical enzymes of the innate immune system". Proteins 72 (2): 589–605. doi:10.1002/prot.21950. PMID 18247411. 

External links[edit]

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External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002007

Peroxidases are haem-containing enzymes that use hydrogen peroxide as the electron acceptor to catalyse a number of oxidative reactions.

Peroxidases are found in bacteria, fungi, plants and animals. On the basis of sequence similarity, a number of animal haem peroxidases can be categorised as members of a superfamily: myeloperoxidase (MPO); eosinophil peroxidase (EPO); lactoperoxidase (LPO); thyroid peroxidase (TPO); prostaglandin H synthase (PGHS); and peroxidasin [PUBMED:8062820, PUBMED:7922023, PUBMED:2840655].

MPO plays a major role in the oxygen-dependent microbicidal system of neutrophils. EPO from eosinophilic granulocytes participates in immunological reactions, and potentiates tumor necrosis factor (TNF) production and hydrogen peroxide release by human monocyte-derived macrophages [PUBMED:2548579, PUBMED:7774640]. In the main, MPO (and possibly EPO) utilises Cl-ions and H2O2 to form hypochlorous acid (HOCl), which can effectively kill bacteria or parasites. In secreted fluids, LPO catalyses the oxidation of thiocyanate ions (SCN-) by H2O2, producing the weak oxidising agent hypothiocyanite (OSCN-), which has bacteriostatic activity [PUBMED:6295491]. TPO uses I- ions and H2O2 to generate iodine, and plays a central role in the biosynthesis of thyroid hormones T(3) and T(4).

To date, the 3D structures of MPO and PGHS have been reported. MPO is a homodimer: each monomer consists of a light (A or B) and a heavy (C or D) chain resulting from post-translational excision of 6 residues from the common precursor. Monomers are linked by a single inter-chain disulphide. Each monomer includes a bound calcium ion [PUBMED:1320128]. PGHS exists as a symmetric dimer, each monomer of which consists of 3 domains: an N-terminal epidermal growth factor (EGF) like module; a membrane-binding domain; and a large C-terminal catalytic domain containing the cyclooxygenase and the peroxidase active sites. The catalytic domain shows striking structural similarity to MPO. The cyclooxygenase active site, which catalyses the formation of prostaglandin G2 (PGG2) from arachidonic acid, resides at the apex of a long hydrophobic channel, extending from the membrane-binding domain to the centre of the molecule. The peroxidase active site, which catalyses the reduction of PGG2 to PGH2, is located on the other side of the molecule, at the haem binding site [PUBMED:8121489]. Both MPO and the catalytic domain of PGHS are mainly alpha-helical, 19 helices being identified as topologically and spatially equivalent; PGHS contains 5 additional N-terminal helices that have no equivalent in MPO. In both proteins, three Asn residues in each monomer are glycosylated.

Gene Ontology

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Domain organisation

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Representative proteomes NCBI
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Meta
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RP35
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RP55
(1103)
RP75
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  Seed
(123)
Full
(2338)
Representative proteomes NCBI
(2365)
Meta
(62)
RP15
(473)
RP35
(646)
RP55
(1103)
RP75
(1401)
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Curation and family details

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Seed source: Prosite
Previous IDs: none
Type: Family
Author: Bateman A
Number in seed: 123
Number in full: 2338
Average length of the domain: 385.50 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 55.96 %

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 19.3 19.3
Trusted cut-off 19.7 19.8
Noise cut-off 19.0 19.1
Model length: 530
Family (HMM) version: 10
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Interactions

There are 2 interactions for this family. More...

An_peroxidase EGF

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 An_peroxidase domain has been found. There are 314 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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