{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:23:05Z","timestamp":1789647785743,"version":"4.0.0"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,8,4]],"date-time":"2019-08-04T00:00:00Z","timestamp":1564876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI137056"],"award-info":[{"award-number":["R01AI137056"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Protein disulfide isomerase (PDI) is mainly located in the endoplasmic reticulum (ER) but is also secreted into the bloodstream where its oxidoreductase activity is involved with thrombus formation. Quercetin-3-rutinoside (Q3R) blocks this activity, but its inhibitory mechanism against PDI is not fully understood. Here, we examined the potential inhibitory effect of Q3R on another process that requires PDI: disassembly of the multimeric cholera toxin (CT). In the ER, PDI physically displaces the reduced CTA1 subunit from its non-covalent assembly in the CT holotoxin. This is followed by CTA1 dislocation from the ER to the cytosol where the toxin interacts with its G protein target for a cytopathic effect. Q3R blocked the conformational change in PDI that accompanies its binding to CTA1, which, in turn, prevented PDI from displacing CTA1 from its holotoxin and generated a toxin-resistant phenotype. Other steps of the CT intoxication process were not affected by Q3R, including PDI binding to CTA1 and CT reduction by PDI. Additional experiments with the B chain of ricin toxin found that Q3R could also disrupt PDI function through the loss of substrate binding. Q3R can thus inhibit PDI function through distinct mechanisms in a substrate-dependent manner.<\/jats:p>","DOI":"10.3390\/toxins11080458","type":"journal-article","created":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T03:25:22Z","timestamp":1564975522000},"page":"458","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Quercetin-3-Rutinoside Blocks the Disassembly of Cholera Toxin by Protein Disulfide Isomerase"],"prefix":"10.3390","volume":"11","author":[{"given":"Jessica","family":"Guyette","sequence":"first","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Cherubin","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Serrano","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Taylor","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1864-175X","authenticated-orcid":false,"given":"Faisal","family":"Abedin","sequence":"additional","affiliation":[{"name":"Department of Physics, College of Sciences, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Burress","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suren A.","family":"Tatulian","sequence":"additional","affiliation":[{"name":"Department of Physics, College of Sciences, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4176-9361","authenticated-orcid":false,"given":"Ken","family":"Teter","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/B978-0-12-800188-2.00007-0","article-title":"Vibrio choleraeand Escherichia coli heat-labile enterotoxins and beyond","volume":"Volume 4","author":"Heggelund","year":"2015","journal-title":"The Comprehensive Sourcebook of Bacterial Protein Toxins"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Cho, J.A., Chinnapen, D.J., Aamar, E., Welscher, Y.M., Lencer, W.I., and Massol, R. 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