828813861ENSG00000121053ENSMUSG00000052234P11678P49290NM_000502NM_007946NP_000493NP_031972Eosinophil peroxidase is an enzyme found within the eosinophil granulocytes, innate immune cells of humans and mammals.

The major function of eosinophil peroxidase is to catalyze the formation of hypohalous acids from hydrogen peroxide and halide ions in solution.

[a] However, the role of eosinophilic peroxidase seems to be to generate hyphalous acids largely from bromide and iodide rather than chloride, since the former are favored greatly over the latter.

The open reading frame of human eosinophil peroxidase was found to have a length of 2,106 base pairs (bp).

The precursor protein goes through the following processing steps before becoming active: Unlike MPO, heme in EPO is not linked via methionine.

The core of the catalytic domain surrounding the active site consists of six α-helices, five from the heavy polypeptide chain and one from the light.

Ligands are provided by serine and threonine hydroxyl; backbone carbonyl; and carboxylic acid groups, one of which comes from the light polypeptide chain.

However, a direct correspondence between the absorption spectra of EPO, TPO and LPO as well as high sequence similarity allows us to compare the properties of the three.

Structural features which are highly necessary for function are subjected to strong conservation pressure, while regions distant from the active site undergo genetic drift.

[9] The active site of eosinophil peroxidase contains a single iron atom in tetradentate complexation with a protoporphyrin IX cofactor.

[9] For comparison, in myeloperoxidase, there is a third attachment point, Met243 forming a sulphonium ion bridge with the pendant vinyl group on heme.

These include a short water network comprising five molecules; stabilized by hydrogen bonding with histidine, glutamine, and arginine residues.

The crystal structures of MPO have been solved both in native states and with inhibitors bound and are deposited in the Protein Data Bank under the accession numbers 1CXP, 1D5L, 1D2V, and 1D7W.

However, there is a second cycle wherein compound I can proceed via two one-electron reduction steps to oxidize arbitrary substrates to their radical forms.

Eosinophil peroxidase has been demonstrated to oxidize tyrosine residues on proteins, which has also been implicated in reactive oxygen signalling cascades.

[9] The mutant of MPO wherein heme-linked Met243 was mutated nonconservatively showed a lack of chlorination ability, implicating this residue or its peculiar functional group in substrate specificity.

[16] Large multicellular organisms engage multiple systems as defensive efforts against infecting bacteria or invading parasites.

One strategy, which falls under the domain of cellular immunity, depends on the action of enzymes which catalyze the peroxidase reaction.

[18] Eosinophils form part of the myelocytic lineage, one of two major classes of bone-marrow-derived cell types (along with the lymphocytes) which circulate in the blood and lymph and play critical roles in immune responses.

Having diverged from myeloperoxidase and lactoperoxidase, these three enzymes now perform distinct but not non-overlapping roles; lactoperoxidase helps maintain the sterility of mammalian milk; myeloperoxidase and eosinophil peroxidase inhabit granules and play roles in host defense—an example of how the concept of a single chemical function can be harnessed in myriad ways in nature.

[20] Early studies on myeloperoxidase deficiency revealed that the most common disease variants were missense mutations, including that of the heme-linked methionine residue.