| http://purl.uniprot.org/citations/29191937 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29191937 | http://www.w3.org/2000/01/rdf-schema#comment | "Protein-disulfide isomerase (PDI) is a ubiquitous dithiol-disulfide oxidoreductase that performs an array of cellular functions, such as cellular signaling and responses to cell-damaging events. PDI can become dysfunctional by post-translational modifications, including those promoted by biological oxidants, and its dysfunction has been associated with several diseases in which oxidative stress plays a role. Because the kinetics and products of the reaction of these oxidants with PDI remain incompletely characterized, we investigated the reaction of PDI with the biological oxidant peroxynitrite. First, by determining the rate constant of the oxidation of PDI's redox-active Cys residues (Cys53 and Cys397) by hydrogen peroxide (k = 17.3 ± 1.3 m-1 s-1 at pH 7.4 and 25 °C), we established that the measured decay of the intrinsic PDI fluorescence is appropriate for kinetic studies. The reaction of these PDI residues with peroxynitrite was considerably faster (k = (6.9 ± 0.2) × 104 m-1 s-1), and both Cys residues were kinetically indistinguishable. Limited proteolysis, kinetic simulations, and MS analyses confirmed that peroxynitrite preferentially oxidizes the redox-active Cys residues of PDI to the corresponding sulfenic acids, which reacted with the resolving thiols at the active sites to produce disulfides (i.e. Cys53-Cys56 and Cys397-Cys400). A fraction of peroxynitrite, however, decayed to radicals that hydroxylated and nitrated other active-site residues (Trp52, Trp396, and Tyr393). Excess peroxynitrite promoted further PDI oxidation, nitration, inactivation, and covalent oligomerization. We conclude that these PDI modifications may contribute to the pathogenic mechanism of several diseases associated with dysfunctional PDI."xsd:string |
| http://purl.uniprot.org/citations/29191937 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m117.807016"xsd:string |
| http://purl.uniprot.org/citations/29191937 | http://purl.uniprot.org/core/author | "Augusto O."xsd:string |
| http://purl.uniprot.org/citations/29191937 | http://purl.uniprot.org/core/author | "Iqbal A."xsd:string |
| http://purl.uniprot.org/citations/29191937 | http://purl.uniprot.org/core/author | "Laurindo F.R.M."xsd:string |
| http://purl.uniprot.org/citations/29191937 | http://purl.uniprot.org/core/author | "Geyer R.R."xsd:string |
| http://purl.uniprot.org/citations/29191937 | http://purl.uniprot.org/core/author | "Truzzi D.R."xsd:string |
| http://purl.uniprot.org/citations/29191937 | http://purl.uniprot.org/core/author | "Peixoto A.S."xsd:string |
| http://purl.uniprot.org/citations/29191937 | http://purl.uniprot.org/core/author | "Soares Moretti A.I."xsd:string |
| http://purl.uniprot.org/citations/29191937 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/29191937 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/29191937 | http://purl.uniprot.org/core/pages | "1450-1465"xsd:string |
| http://purl.uniprot.org/citations/29191937 | http://purl.uniprot.org/core/title | "Peroxynitrite preferentially oxidizes the dithiol redox motifs of protein-disulfide isomerase."xsd:string |
| http://purl.uniprot.org/citations/29191937 | http://purl.uniprot.org/core/volume | "293"xsd:string |
| http://purl.uniprot.org/citations/29191937 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/29191937 |
| http://purl.uniprot.org/citations/29191937 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/29191937 |
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| http://purl.uniprot.org/uniprot/#_B4DNP9-mappedCitation-29191937 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29191937 |
| http://purl.uniprot.org/uniprot/#_B3KTQ9-mappedCitation-29191937 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29191937 |
| http://purl.uniprot.org/uniprot/#_B4DJS0-mappedCitation-29191937 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29191937 |
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| http://purl.uniprot.org/uniprot/#_P07237-mappedCitation-29191937 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29191937 |