Haem peroxidase, animal <p>Peroxidases are haem-containing enzymes that use hydrogen peroxide asthe electron acceptor to catalyse a number of oxidative reactions.</p><p>Peroxidases are found in bacteria, fungi, plants and animals. On the basisof sequence similarity, a number of animal haem peroxidases can becategorised as members of a superfamily: myeloperoxidase (MPO); eosinophilperoxidase (EPO); lactoperoxidase (LPO); thyroid peroxidase (TPO);prostaglandin H synthase (PGHS); and peroxidasin [<cite idref="PUB00001259"/>, <cite idref="PUB00005246"/>, <cite idref="PUB00004979"/>]. </p><p>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 [<cite idref="PUB00000306"/>, <cite idref="PUB00001479"/>]. 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 [<cite idref="PUB00000580"/>]. 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). </p><p>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 [<cite idref="PUB00003292"/>]. PGHS exists as a symmetric dimer, each monomer of which consists of 3 domains: an N-terminal epidermalgrowth factor (EGF) like module; a membrane-binding domain; and a largeC-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 thecentre of the molecule. The peroxidase active site, which catalyses thereduction of PGG2 to PGH2, is located on the other side of the molecule, atthe haem binding site [<cite idref="PUB00004165"/>]. Both MPO and the catalytic domain of PGHS are mainly alpha-helical, 19 helices being identified as topologically andspatially equivalent; PGHS contains 5 additional N-terminal helices thathave no equivalent in MPO. In both proteins, three Asn residues in eachmonomer are glycosylated.</p>