Myeloperoxidase

1CXP, 1D2V, 1D5L, 1D7W, 1DNU, 1DNW, 1MHL, 1MYP, 3F9P, 3ZS0, 3ZS1, 4DL1, 4EJX, 4C1M, 5FIW435317523ENSG00000005381ENSMUSG00000009350P05164P11247NM_000250NM_010824NP_000241NP_034954Myeloperoxidase (MPO) is a peroxidase enzyme that in humans is encoded by the MPO gene on chromosome 17. MPO is most abundantly expressed in neutrophil granulocytes (a subtype of white blood cells), and produces hypohalous acids to carry out their antimicrobial activity. It is a lysosomal protein stored in azurophilic granules of the neutrophil and released into the extracellular space during degranulation. Neutrophil myeloperoxidase has a heme pigment, which causes its green color in secretions rich in neutrophils, such as pus and some forms of mucus. The green color contributed to its outdated name verdoperoxidase.1cxp: CRYOGENIC CRYSTAL STRUCTURE OF HUMAN MYELOPEROXIDASE ISOFORM C1d2v: CRYSTAL STRUCTURE OF BROMIDE-BOUND HUMAN MYELOPEROXIDASE ISOFORM C AT PH 5.51d5l: CRYSTAL STRUCTURE OF CYANIDE-BOUND HUMAN MYELOPEROXIDASE ISOFORM C AT PH 5.51d7w: CRYSTAL STRUCTURE OF HUMAN MYELOPEROXIDASE ISOFORM C COMPLEXED WITH CYANIDE AND BROMIDE AT PH 4.01dnu: STRUCTURAL ANALYSES OF HUMAN MYELOPEROXIDASE-THIOCYANATE COMPLEX1dnw: HUMAN MYELOPEROXIDASE-CYANIDE-THIOCYANATE COMPLEX1mhl: CRYSTAL STRUCTURE OF HUMAN MYELOPEROXIDASE ISOFORM C CRYSTALLIZED IN SPACE GROUP P2(1) AT PH 5.5 AND 20 DEG C1myp: X-RAY CRYSTAL STRUCTURE OF CANINE MYELOPEROXIDASE AT 3 ANGSTROMS RESOLUTION Myeloperoxidase (MPO) is a peroxidase enzyme that in humans is encoded by the MPO gene on chromosome 17. MPO is most abundantly expressed in neutrophil granulocytes (a subtype of white blood cells), and produces hypohalous acids to carry out their antimicrobial activity. It is a lysosomal protein stored in azurophilic granules of the neutrophil and released into the extracellular space during degranulation. Neutrophil myeloperoxidase has a heme pigment, which causes its green color in secretions rich in neutrophils, such as pus and some forms of mucus. The green color contributed to its outdated name verdoperoxidase. The 150-kDa MPO protein is a cationic homodimer consisting of two 15-kDa light chains and two variable-weight glycosylated heavy chains bound to a prosthetic heme group. The light chains are glycosylated and contain the modified iron protoporphyrin IX active site. Together, the light and heavy chains form two identical 73-kDa monomers connected by a cystine bridge at Cys153. The protein forms a deep crevice which holds the heme group at the bottom, as well as a hydrophobic pocket at the entrance to the distal heme cavity which carries out its catalytic activity. Three isoforms have been identified, differing only in the size of the heavy chains. One of the ligands is the carbonyl group of Asp 96. Calcium-binding is important for structure of the active site because of Asp 96's close proximity to the catalytic His95 side chain. MPO is a member of the XPO subfamily of peroxidases and produces hypochlorous acid (HOCl) from hydrogen peroxide (H2O2) and chloride anion (Cl−) (or hypobromous acid if Br- is present) during the neutrophil's respiratory burst. It requires heme as a cofactor. Furthermore, it oxidizes tyrosine to tyrosyl radical using hydrogen peroxide as an oxidizing agent. Hypochlorous acid and tyrosyl radical are cytotoxic, so they are used by the neutrophil to kill bacteria and other pathogens. However, this hypochlorous acid may also cause oxidative damage in host tissue. Moreover, MPO oxidation of apoA-I reduces HDL-mediated inhibition of apoptosis and inflammation. In addition, MPO mediates protein nitrosylation and the formation of 3-chlorotyrosine and dityrosine crosslinks. Myeloperoxidase deficiency is a hereditary deficiency of the enzyme, which predisposes to immune deficiency. Antibodies against MPO have been implicated in various types of vasculitis, most prominently three clinically and pathologically recognized forms: granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis), microscopic polyangiitis (MPA); and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome). Antibodies are also known as anti-neutrophil cytoplasmic antibodies (ANCAs), though ANCAs have also been detected in staining of the perinuclear region. Recent studies have reported an association between elevated myeloperoxidase levels and the severity of coronary artery disease. And Heslop et al. reported that elevated MPO levels more than doubled the risk for cardiovascular mortality over a 13-year period. It has also been suggested that myeloperoxidase plays a significant role in the development of the atherosclerotic lesion and rendering plaques unstable. An initial 2003 study suggested that MPO could serve as a sensitive predictor for myocardial infarction in patients presenting with chest pain. Since then, there have been over 100 published studies documenting the utility of MPO testing. The 2010 Heslop et al. study reported that measuring both MPO and CRP (C-reactive protein; a general and cardiac-related marker of inflammation) provided added benefit for risk prediction than just measuring CRP alone.