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• W2072845970 abstract "The optimal level of oxygen-dependent microbicidal activity in human neutrophils depends on the generation of highly toxic products, including hypochlorous acid, by hydrogen peroxide in the presence of chloride anion and the neutrophil granule protein myeloperoxidase (MPO). The biosynthesis of MPO is normally restricted to the promyelocytic stage of myeloid development and includes N-linked glycosylation, heme insertion, proteolytic processing, subunit dimerization, and eventual targeting to the azurophilic granule. In the endoplasmic reticulum, MPO precursors interact transiently with calreticulin and calnexin, presumably in their capacity as molecular chaperones. In light of the important role of the MPO-H2O2-chloride system in human host defense, the relatively high prevalence of inherited MPO deficiency was an unanticipated insight provided by the widespread use of automated flow cytometry for the enumeration of leukocytes in clinical specimens. In many cases of inherited MPO deficiency, affected neutrophils have immunochemical evidence of precursor protein but lack the subunits of mature MPO, peroxidase activity, or the ability to chlorinate target proteins. To date, four genotypes have been reported to cause inherited MPO deficiency, each of which results in missense mutations. In the genotype Y173C, the mutant precursor is retained in the endoplasmic reticulum by virtue of its prolonged interaction with calnexin, and it eventually undergoes degradation in the 20S proteasome. In this way, the quality control system operating in the endoplasmic reticulum retrieves malfolded MPO precursors from the biosynthetic pathway and creates the biochemical phenotype of MPO deficiency. Thus MPO deficiency caused by Y173C joins the ranks of cystic fibrosis, protein C deficiency, and other genetic disorders that reflect abnormalities in protein folding." @default.
• W2072845970 created "2016-06-24" @default.
• W2072845970 creator A5089063045 @default.
• W2072845970 date "1999-09-01" @default.
• W2072845970 modified "2023-09-24" @default.
• W2072845970 title "Quality control in the endoplasmic reticulum: Lessons from hereditary myeloperoxidase deficiency" @default.
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• W2072845970 doi "https://doi.org/10.1016/s0022-2143(99)90200-7" @default.
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