Animal heme-dependent peroxidases

Pfam_box
Symbol = An_peroxidase
Name = Animal haem peroxidase


width =
caption =
Pfam= PF03098
InterPro= IPR002007
SMART=
PROSITE = PDOC00394
SCOP = 1mhl
TCDB =
OPM family= 37
OPM protein= 1q4g
PDB=PDB3|1mhlA:171-270 PDB3|1dnuC:279-721 PDB3|1d7wC:279-721PDB3|1d2vA:171-270 PDB3|1dnwA:171-270 PDB3|1cxpD:279-721PDB3|1d5lA:171-270 PDB3|1mypD:280-721 PDB3|1v0xA:450-507PDB3|1pxxB:450-507 PDB3|3pghA:450-507 PDB3|4coxD:450-507PDB3|1ddxC:450-507 PDB3|5coxC:450-507 PDB3|1cvuA:450-507PDB3|6coxB:450-507 PDB3|1dd0A:450-507 PDB3|1cx2C:450-507PDB3|1dcxA:450-507 PDB3|1pgfB:131-583 PDB3|1pgeA:131-583PDB3|1igzA:131-586 PDB3|1pthA:131-583 PDB3|1prhB:131-586PDB3|1q4gB:131-584 PDB3|1pggA:131-583 PDB3|1ht8A:131-583PDB3|1ebvA:131-583 PDB3|1fe2A:131-586 PDB3|1ht5B:131-583PDB3|1eqhB:131-586 PDB3|1cqeB:131-586 PDB3|2aylB:131-584PDB3|1diyA:131-584 PDB3|1igxA:131-586 PDB3|1u67A:131-586PDB3|1eqgA:131-586 PDB3|1djjA:131-583

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 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 peroxidasincite 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] 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 |doi=10.1016/S0969-2126(00)00046-0] 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 |doi=10.1002/prot.340030206] .

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 macrophagescite journal |author=Kimura S, Hong YS, Kotani T, Ohtaki S, Kikkawa F |title=Structure of the human thyroid peroxidase gene: comparison and relationshipto the human myeloperoxidase gene |journal=Biochemistry |volume=28 |issue=10 |pages=4481–4489 |year=1989 |pmid=2548579 |doi=10.1021/bi00436a054] 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 |doi=10.1002/eji.1830250535] . Inthe 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 activitycite 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] . 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).

tructure

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 ioncite 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 |doi=10.1016/0022-2836(92)90133-5] . 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 sitecite 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 |doi=10.1038/367243a0] . 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; -> Reference 9.

References

9. Zamocky M, Jakopitsch C, Furtmueller PG, Dunand C, and Obinger C:"The peroxidase-cyclooxygenase superfamily. Reconstructed evolution of critical enzyme of the innate immune system." Proteins 2008 Feb 4 DOI 10.1002/prot.21950

systematic analysis - see: http://peroxibase.isb-sib.ch/