Summary: Animal haem peroxidase
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Animal heme-dependent peroxidases Edit Wikipedia article
|Animal heme-dependent peroxidase|
|SCOP2||1mhl / SCOPe / SUPFAM|
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.
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. MPO (and possibly EPO) primarily use Clâˆ’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 (SCNâˆ’) by H2O2, producing the weak oxidizing agent hypothiocyanite (OSCNâˆ’), which has bacteriostatic activity. TPO uses Iâˆ’ ions and H2O2 to generate iodine, and plays a central role in the biosynthesis of thyroid hormones T3 and T4. Myeloperoxidase ( â€‹), for example, resides in the human nucleus and lysosome and acts as a defense response to oxidative stress, preventing apoptosis of the cell.
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. PGHS exists as a symmetric homodimer, 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.
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. 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
The following is a list of human proteins containing this domain:
- doi:10.1021/bi0111808. PMIDÂ 11705390. â€‹; 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): 13990â€“7.
- 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): 3438â€“3447. doi:10.1002/j.1460-2075.1994.tb06649.x. PMCÂ 395246. PMIDÂ 8062820.
- Poulos TL, Li H (1994). "Structural variation in heme enzymes: a comparative analysis of peroxidase and P450 crystal structures". Structure. 2 (6): 461â€“464. doi:10.1016/S0969-2126(00)00046-0. PMIDÂ 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): 113â€“120. doi:10.1002/prot.340030206. PMIDÂ 2840655. S2CIDÂ 29575992.
- 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): 4481â€“4489. doi:10.1021/bi00436a054. PMIDÂ 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): 1366â€“1373. doi:10.1002/eji.1830250535. PMIDÂ 7774640. S2CIDÂ 33362887.
- Wever R, Kast WM, Kasinoedin JH, Boelens R (1982). "The peroxidation of thiocyanate catalysed by myeloperoxidase and lactoperoxidase". Biochim. Biophys. Acta. 709 (2): 212â€“219. doi:10.1016/0167-4838(82)90463-0. PMIDÂ 6295491.
- Fenna RE, Zeng J (1992). "X-ray crystal structure of canine myeloperoxidase at 3 A resolution". J. Mol. Biol. 226 (1): 185â€“207. doi:10.1016/0022-2836(92)90133-5. PMIDÂ 1320128.
- Picot D, Loll PJ, Garavito RM (1994). "The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1". Nature. 367 (6460): 243â€“249. Bibcode:1994Natur.367..243P. doi:10.1038/367243a0. PMIDÂ 8121489. S2CIDÂ 4340064.
- Zamocky M, Jakopitsch C, FurtmÃ¼ller PG, Dunand C, Obinger C (August 2008). "The peroxidase-cyclooxygenase superfamily: Reconstructed evolution of critical enzymes of the innate immune system". Proteins. 72 (2): 589â€“605. doi:10.1002/prot.21950. PMIDÂ 18247411. S2CIDÂ 19832239.
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Animal haem peroxidase Provide feedback
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External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR019791
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 H 2 O 2 to form hypochlorous acid (HOCl), which can effectively kill bacteria or parasites. In secreted fluids, LPO catalyses the oxidation of thiocyanate ions (SCN - ) by H 2 O 2 , producing the weak oxidising agent hypothiocyanite (OSCN - ), which has bacteriostatic activity [ PUBMED:6295491 ]. TPO uses I - ions and H 2 O 2 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.
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|Number in seed:||330|
|Number in full:||13653|
|Average length of the domain:||360.70 aa|
|Average identity of full alignment:||20 %|
|Average coverage of the sequence by the domain:||52.49 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||18|
|Download:||download the raw HMM for this family|
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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 An_peroxidase domain has been found. There are 608 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.