Summary: Animal haem peroxidase

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Wikipedia: Animal heme-dependent peroxidases
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Animal heme-dependent peroxidases Edit Wikipedia article

Animal heme-dependent peroxidase

Crystal structure of the human myeloperoxidase-thiocyanate complex.^[1]

Identifiers

Symbol

An_peroxidase

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

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]

[edit] Function

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]

[edit] Structure

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]

[edit] Active site

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.

[edit] Human proteins containing this domain

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

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

[edit] References

^ ^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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.

[edit] External links

Dunand C. "PeroxiBase - The peroxidase database". Swiss Institute of Bioinformatics. Archived from the original on 13 October 2008. Retrieved 2008-11-21.

C Frank. "MolProbity Ramachandran analysis, 1dnu". PDB. Retrieved 2008-11-21.

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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.

Animal haem peroxidase Provide feedback

No Pfam abstract.

External database links

PANDIT:	PF03098
PRINTS:	PR00457
PROSITE:	PDOC00394
Pseudofam:	PF03098
SCOP:	1mhl
SYSTERS:	An_peroxidase

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

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Molecular function	heme binding (GO:0020037)
	peroxidase activity (GO:0004601)
Biological process	response to oxidative stress (GO:0006979)
	oxidation-reduction process (GO:0055114)

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

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Pfam viewer: an HTML-based viewer that uses DAS to retrieve alignment fragments on request

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

	Seed (123)	Full (2338)	Representative proteomes				NCBI (2365)	Meta (62)
	Seed (123)	Full (2338)	RP15 (473)	RP35 (646)	RP55 (1103)	RP75 (1401)	NCBI (2365)	Meta (62)
Jalview	View	View	View	View	View	View	View	View
HTML	View	View	View	View	View	View
PP/heatmap	₁	View	View	View	View	View
Pfam viewer	View	View

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (123)	Full (2338)	Representative proteomes				NCBI (2365)	Meta (62)
	Seed (123)	Full (2338)	RP15 (473)	RP35 (646)	RP55 (1103)	RP75 (1401)	NCBI (2365)	Meta (62)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (123)	Full (2338)	Representative proteomes				NCBI (2365)	Meta (62)
	Seed (123)	Full (2338)	RP15 (473)	RP35 (646)	RP55 (1103)	RP75 (1401)	NCBI (2365)	Meta (62)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	Download	Download	Download	Download	Download

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

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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.

Curation

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

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

Download:

download the raw HMM for this family

Species distribution

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Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

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Interactions

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

EGF An_peroxidase

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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Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: An_peroxidase (PF03098)

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