Protein Disulfide Isomerase
The dithiol-disulfide oxidoreductase protein disulfide isomerase (PDI) was discovered in 1963 as the first protein folding chaperone. Research groups led by Brunó Straub (Venetianer and Straub 1963) and Christian B. Anfinsen (Goldberger et al. 1963) independently made pivotal discoveries about an enzyme that reactivated reduced ribonuclease. Straub and coworkers purified the reactivating system from chicken pancreas. Anfinsen studied the system in conjunction with his Nobel-prize-winning work on ribonuclease and purified a system with similar activity from rat liver microsomes. In 1972, the enzyme was given the name protein disulfide isomerase and its official classification number, EC 220.127.116.11. The newly purified protein was identified as the “ribonuclease-reactivating enzyme” and was nearly identical to glutathione-insulin transhydrogenase, causing confusion in the field (Bjelland et al. 1983). Both enzymes...
We acknowledge financial support from the National Cancer Institute, NIH (CA193690).
- Bjelland S, Wallevik K, Kroll J, Dixon JE, Morin JE, Freedman RB, Lambert N, Varandani PT, Nafz MA. Immunological identity between bovine preparations of thiol-protein-disulfide oxidoreductase, glutathione-insulin transhydrogenase and protein-disulfide isomerase. Biochim Biophys Acta. 1983;747:197–9.CrossRefPubMedGoogle Scholar
- Montane J, de Pablo S, Obach M, Cadavez L, Castano C, Alcarraz-Vizan G, Visa M, Rodriguez-Comas J, Parrizas M, Servitja JM, Novials A. Protein disulfide isomerase ameliorates beta-cell dysfunction in pancreatic islets overexpressing human islet amyloid polypeptide. Mol Cell Endocrinol. 2016;420:57–65.CrossRefPubMedGoogle Scholar
- Reinhardt C, von Brühl ML, Manukyan D, Grahl L, Lorenz M, Altmann B, Dlugai S, Hess S, Konrad I, Orschiedt L, Machman N, Ruddock L, Massberg S, Engelmann B. Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation. J Clin Invest. 2008;118:1110–22.PubMedPubMedCentralGoogle Scholar
- Vatolin S, Phillips JG, Jha BK, Govindgari S, Hu J, Grabowski D, Parker Y, Lindner DJ, Zhong F, Distelhorst CW, Smith MR, Cotta C, Xu Y, Chilakala S, Kuang RR, Tall S, Reu FJ. Novel protein disulfide isomerase inhibitor with anticancer activity in multiple myeloma. Cancer Res. 2016;76:3340–50.CrossRefPubMedGoogle Scholar
- Vuori K, Pihlajaniemi T, Marttila M, Kivirikko KI. Characterization of the human prolyl 4-hydroxylase tetramer and its multifunctional protein disulfide-isomerase subunit synthesized in a baculovirus expression system. Proc Natl Acad Sci U S A. 1992;89:7467–70.PubMedPubMedCentralCrossRefGoogle Scholar
- Woehlbier U, Colombo A, Saaranen MJ, Perez V, Ojeda J, Bustos FJ, Andreu CI, Torrez M, Valenzuela V, Medinas DB, Rozas P, Vidal RL, Lopez-Gonzalez R, Salameh J, Fernandez-Collemann S, Munoz N, Matus S, Armisen R, Sagredo A, Palma K, Irrazabal T, Almeida S, Gonzalez-Perez P, Campero M, Gao FB, Henny P, van Zundert B, Ruddock LW, Concha ML, Henriquez JP, Brown RH, Hetz C. ALS-linked protein disulfide isomerase variants cause motor dysfunction. EMBO J. 2016;35:845–65.PubMedPubMedCentralCrossRefGoogle Scholar
- Xu S, Butkevich AN, Yamada R, Zhou Y, Debnath B, Duncan R, Zandi E, Petasis NA, Neamati N. Discovery of an orally active small-molecule irreversible inhibitor of protein disulfide isomerase for ovarian cancer treatment. Proc Natl Acad Sci U S A. 2012;109:16348–53.PubMedPubMedCentralCrossRefGoogle Scholar