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 production and hydrogen peroxide release by human monocyte-derived macrophages. MPO primarily use Cl−ions and H2O2 to form hypochlorous acid, which can effectively kill bacteria or parasites. In secreted fluids, LPO catalyses the oxidation of thiocyanate ions by H2O2, producing the weak oxidizing agenthypothiocyanite, which has bacteriostatic activity. TPO uses I− ions and H2O2 to generate iodine, and plays a central role in the biosynthesis of thyroid hormones T3 and T4. Myeloperoxidase, for example, resides in the human nucleus and lysosome and acts as a defense response to oxidative stress, preventing apoptosis of the cell.
Structure
3D structures of MPO and PGHS have been reported. MPO is a homodimer: each monomer consists of a light and a heavy 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 boundcalcium ion. PGHS exists as a symmetric homodimer, each monomer of which consists of 3 domains: an N-terminal epidermal growth factor like module; a membrane-binding domain; and a large C-terminal catalytic domain containing the cyclooxygenase and the peroxidaseactive 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.
Active site
The cyclooxygenase active site, which catalyzes the formation of prostaglandin G2 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.
