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Pdi p567844/6/2023 PDI only interacts covalently with the cysteines of its substrates, but also binds a variety of peptides/proteins and small chemical ligands such as thyroid hormone. PDI has multiple roles, acting as a chaperone, a binding partner of other proteins, and a hormone reservoir as well as a disulfide isomerase in the formation of disulfide bonds. Protein disulfide isomerase (PDI) is a folding assistant in the endoplasmic reticulum (ER) of eukaryotic cells. Susumu Imaoka, in International Review of Cell and Molecular Biology, 2011 Abstract To date, no one has been able to generate a PDI-deficient mouse model, possibly due to the critical role of PDI during cell growth, proliferation, and differentiation. PDI knockdown using small-interfering RNA (siRNA) determined that PDI has a protective effect on endothelial cells under both normoxia and hypoxia conditions. PDI also functions as a molecular chaperone by binding polypeptides and preventing protein aggregation, and the combination of its redox and chaperone activities is what makes PDI an effective and important enzyme in oxidative protein folding. PDI contains a typical thioredoxin active site, which contains two cysteines separated by two other amino acid residues (the CXXC motif). Its major function is to catalyze disulfide bond formation in newly synthesized proteins and, importantly, high concentrations of Ca 2+ augment this activity. PDI is an abundant and versatile redox enzyme that has oxidase, reductase and isomerase activity and interacts with a variety of substrates and is widely distributed in the ER lumen. The C-terminus of the protein contains numerous pairs of acidic residues that form the low affinity, high capacity Ca 2+ binding sites. PDI is a 58-kDa Ca 2+-binding chaperone that binds 19 mol of Ca 2+ per mol of protein with low affinity ( K d = 2–5 mM). During protein folding, PDI catalyzes the formation of native disulfide bonds and disulfide bond rearrangement. It comprises approximately 0.8% of total cellular protein and attains near millimolar concentrations in the ER lumen of some tissues. PDI is a ubiquitously expressed multifunctional protein found in the ER. Michalak, in Encyclopedia of Biological Chemistry (Second Edition), 2013 PDI
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