View source for Animal heme-dependent peroxidases

{{Pfam_box
| Symbol = An_peroxidase
| Name = Animal haem peroxidase
| image =
| width =
| caption =
| Pfam= PF03098
| InterPro= IPR002007
| SMART=
| Prosite = PDOC00394
| SCOP = 1mhl
| TCDB =
| OPM family= 37
| OPM protein= 1q4g
| PDB=
{{PDB3|1mhl}}A:171-270   {{PDB3|1dnu}}C:279-721   {{PDB3|1d7w}}C:279-721
{{PDB3|1d2v}}A:171-270   {{PDB3|1dnw}}A:171-270   {{PDB3|1cxp}}D:279-721
{{PDB3|1d5l}}A:171-270   {{PDB3|1myp}}D:280-721   {{PDB3|1v0x}}A:450-507
{{PDB3|1pxx}}B:450-507   {{PDB3|3pgh}}A:450-507   {{PDB3|4cox}}D:450-507
{{PDB3|1ddx}}C:450-507   {{PDB3|5cox}}C:450-507   {{PDB3|1cvu}}A:450-507
{{PDB3|6cox}}B:450-507   {{PDB3|1dd0}}A:450-507   {{PDB3|1cx2}}C:450-507
{{PDB3|1dcx}}A:450-507   {{PDB3|1pgf}}B:131-583   {{PDB3|1pge}}A:131-583
{{PDB3|1igz}}A:131-586   {{PDB3|1pth}}A:131-583   {{PDB3|1prh}}B:131-586
{{PDB3|1q4g}}B:131-584   {{PDB3|1pgg}}A:131-583   {{PDB3|1ht8}}A:131-583
{{PDB3|1ebv}}A:131-583   {{PDB3|1fe2}}A:131-586   {{PDB3|1ht5}}B:131-583
{{PDB3|1eqh}}B:131-586   {{PDB3|1cqe}}B:131-586   {{PDB3|2ayl}}B:131-584
{{PDB3|1diy}}A:131-584   {{PDB3|1igx}}A:131-586   {{PDB3|1u67}}A:131-586
{{PDB3|1eqg}}A:131-586   {{PDB3|1djj}}A:131-583
}}

'''Animal heme-dependent peroxidases''' is a family of [[peroxidase]]s. 

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); [[Cyclooxygenase|prostaglandin H synthase]] (PGHS); and peroxidasin<ref name="PUB00001259">{{cite journal |author=Nelson RE, Fessler LI, Takagi Y, Blumberg B, Keene DR, Olson PF, Parker CG, Fessler JH |title=Peroxidasin: a novel enzyme-matrix protein of Drosophila development |journal=EMBO J. |volume=13 |issue=15 |pages=3438-3447 |year=1994 |pmid=8062820}}</ref><ref name="PUB00005246">{{cite journal |author=Poulos TL, Li H |title=Structural variation in heme enzymes: a comparative analysis of peroxidase and P450 crystal structures |journal=Structure |volume=2 |issue=6 |pages=461-464 |year=1994 |pmid=7922023}}</ref><ref name="PUB00004979">{{cite journal |author=Kimura S, Ikeda-Saito M |title=Human myeloperoxidase and thyroid peroxidase, two enzymes with separate and distinct physiological functions, are evolutionarily related members of the same gene family |journal=Proteins |volume=3 |issue=2 |pages=113-120 |year=1988 |pmid=2840655}}</ref>.

==Function==
[[Myeloperoxidase]] (MPO) plays a major role in the oxygen-dependent microbicidal system of [[neutrophil]]s. EPO from eosinophilic granulocytes participates in immunological reactions, and potentiates tumor necrosis factor (TNF) production and hydrogen peroxide release by human monocyte-derived macrophages<ref name="PUB00000306">{{cite journal |author=Kimura S, Hong YS, Kotani T, Ohtaki S, Kikkawa F |title=Structure of the human thyroid peroxidase gene: comparison and relationship
to the human myeloperoxidase gene |journal=Biochemistry |volume=28 |issue=10 |pages=4481-4489 |year=1989 |pmid=2548579}}</ref><ref name="PUB00001479">{{cite journal |author=Spessotto P, Dri P, Bulla R, Zabucchi G, Patriarca P |title=Human eosinophil peroxidase enhances tumor necrosis factor and hydrogen peroxide release by human monocyte-derived macrophages |journal=Eur. J. Immunol. |volume=25 |issue=5 |pages=1366-1373 |year=1995 |pmid=7774640}}</ref>. In
the main, MPO (and possibly EPO) utilises Cl<sup>-</sup>ions and H<sub>2</sub>O<sub>2</sub> to form hypochlorous acid (HOCl), which can effectively kill bacteria or parasites. In secreted fluids, LPO catalyses the oxidation of thiocyanate ions (SCN<sup>-</sup>) by H<sub>2</sub>O<sub>2</sub>, producing the weak oxidising agent hypothiocyanite (OSCN<sup>-</sup>), which has bacteriostatic activity<ref name="PUB00000580">{{cite journal |author=Wever R, Kast WM, Kasinoedin JH, Boelens R |title=The peroxidation of thiocyanate catalysed by myeloperoxidase and lactoperoxidase
|journal=Biochim. Biophys. Acta |volume=709 |issue=2 |pages=212-219 |year=1982 |pmid=6295491}}</ref>. TPO uses I<sup>-</sup> ions and H<sub>2</sub>O<sub>2</sub> to generate iodine, and plays a central role in the biosynthesis of thyroid hormones T(3) and T(4).

==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 disulphide. Each monomer includes a bound calcium ion<ref name="PUB00003292">{{cite journal |author=Fenna RE, Zeng J |title=X-ray crystal structure of canine myeloperoxidase at 3 A resolution |journal=J. Mol. Biol. |volume=226 |issue=1 |pages=185-207 |year=1992 |pmid=1320128}}</ref>. 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. 

==Active site==
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<ref name="PUB00004165">{{cite journal |author=Picot D, Loll PJ, Garavito RM |title=The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1 |journal=Nature |volume=367 |issue=6460 |pages=243-249 |year=1994 |pmid=8121489}}</ref>. 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 ==
[[DUOX1]];     [[DUOX2]];     [[EPX]];       [[LPO]];       [[MPO]];       [[PTGS1]];     [[PTGS2]];     [[PXDNL]];
[[TPO]];

==References==
{{reflist|2}}

[[Category:Protein domains]]
[[Category:Protein families]]
[[Category:Integral monotopic proteins]]
[[Category:EC 1.11.1]]

{{InterPro content|IPR002007}}