Animal heme-dependent peroxidases
Encyclopedia
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 heme peroxidases can be categorized 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. MPO (and possibly EPO) primarily use 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 oxidizing agent hypothiocyanite
(OSCN-), which has bacteriostatic activity.TPO uses I- ions and H2O2 to generate iodine, and plays a central role in the biosynthesis of thyroid hormone
s 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.
, 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.
DUOX1
; DUOX2
; EPX
; LPO; MPO
; PTGS1
; PTGS2
; PXDNL; TPO
Peroxidase
Peroxidases are a large family of enzymes that typically catalyze a reaction of the form:For many of these enzymes the optimal substrate is hydrogen peroxide, but others are more active with organic hydroperoxides such as lipid peroxides...
s.
Peroxidases are found in bacteria, fungi, plants and animals. On the basis of sequence similarity, a number of animal heme peroxidases can be categorized as members of a superfamily: myeloperoxidase
Myeloperoxidase
Myeloperoxidase is a peroxidase enzyme that in humans is encoded by the MPO gene. Myeloperoxidase is most abundantly expressed in neutrophil granulocytes . It is a lysosomal protein stored in azurophilic granules of the neutrophil...
(MPO); eosinophil peroxidase (EPO); lactoperoxidase
Lactoperoxidase
Lactoperoxidase is a peroxidase enzyme secreted from mammary, salivary, and other mucosal glands that functions as a natural antibacterial agent. Lactoperoxidase is a member of the heme peroxidase family of enzymes. In humans, lactoperoxidase is encoded by the LPO gene.Lactoperoxidase catalyzes...
(LPO); thyroid peroxidase (TPO); prostaglandin H synthase
Cyclooxygenase
Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain...
(PGHS); and peroxidasin.
Function
MyeloperoxidaseMyeloperoxidase
Myeloperoxidase is a peroxidase enzyme that in humans is encoded by the MPO gene. Myeloperoxidase is most abundantly expressed in neutrophil granulocytes . It is a lysosomal protein stored in azurophilic granules of the neutrophil...
(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. MPO (and possibly EPO) primarily use 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 oxidizing agent hypothiocyanite
Hypothiocyanite
Hypothiocyanite is the anion [OSCN]- and the conjugate base of hypothiocyanous acid. It is an organic compound part of the thiocyanates as it contains the functional group SCN. It is formed when an oxygen is singly bonded to the thiocyanate group...
(OSCN-), which has bacteriostatic activity.TPO uses I- ions and H2O2 to generate iodine, and plays a central role in the biosynthesis of thyroid hormone
Thyroid hormone
The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...
s T3 and T4. Myeloperoxidase
Myeloperoxidase
Myeloperoxidase is a peroxidase enzyme that in humans is encoded by the MPO gene. Myeloperoxidase is most abundantly expressed in neutrophil granulocytes . It is a lysosomal protein stored in azurophilic granules of the neutrophil...
, 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 (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 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 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 (PGG2) from arachidonic acidArachidonic acid
Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...
, 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.
Human proteins containing this domain
The following is a list of human proteins containing this domain:DUOX1
DUOX1
Dual oxidase 1, also known as DUOX1 or ThOX1 , is an enzyme which in humans is encoded by the DUOX1 gene. DUOX1 was first identified in the mammalian thyroid gland. In humans, two isoforms are found; hDUOX1 and hDUOX2...
; DUOX2
DUOX2
Dual oxidase 2, also known as DUOX2 or ThOX2 is an enzyme which in humans is encoded by the DUOX2 gene. Dual oxidase is an enzyme that was first identified in the mammalian thyroid gland. In humans, two isoforms are found; hDUOX1 and hDUOX2...
; EPX
Eosinophil peroxidase
Eosinophil peroxidase is a haloperoxidase enzyme that in humans is encoded by the EPX gene. The enzyme is a heterodimeric 71-77 kD peroxidase consisting of a heavier glycosylated chain and a lighter nonglycosylated chain...
; LPO; MPO
Myeloperoxidase
Myeloperoxidase is a peroxidase enzyme that in humans is encoded by the MPO gene. Myeloperoxidase is most abundantly expressed in neutrophil granulocytes . It is a lysosomal protein stored in azurophilic granules of the neutrophil...
; PTGS1
PTGS1
Cyclooxygenase-1 , also known as prostaglandin G/H synthase 1, prostaglandin-endoperoxide synthase 1 or prostaglandin H2 synthase 1, is an enzyme that in humans is encoded by the PTGS1 gene.- History :...
; PTGS2
PTGS2
Prostaglandin-endoperoxide synthase 2, also known as cyclooxygenase-2 or simply COX-2, is an enzyme that in humans is encoded by the PTGS2 gene.- History :...
; PXDNL; TPO
Thyroid peroxidase
Thyroid peroxidase or thyroperoxidase is an enzyme expressed mainly in the thyroid that liberates iodine for addition onto tyrosine residues on thyroglobulin for the production of thyroxine or triiodothyronine , thyroid hormones. In humans, thyroperoxidase is encoded by the TPO...