Lactoperoxidase (LPO) or salivary peroxidase is found in mammary and salivary gland secretions. It is important for airway antibacterial activity and bacterial clearance []. LPO uses H2O2 to catalyse oxidation of the anion SCN- (thiocyanate) to the antibiotic HOSCN (hypothiocyanous acid) [].
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 [, , ]. 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 [, ]. In the main, MPO (and possibly EPO) utilises Cl-ions and H2O2to 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 []. TPO uses I-ions and H2O2to 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 []. 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 []. Both MPO and the catalytic domain of PGHS are mainly α-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.
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 [, , ]. 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 [, ]. In the main, MPO (and possibly EPO) utilises Cl-ions and H2O2to 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 []. TPO uses I-ions and H2O2to 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 []. 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 []. Both MPO and the catalytic domain of PGHS are mainly α-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.
