{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T17:02:09Z","timestamp":1775581329193,"version":"3.50.1"},"reference-count":118,"publisher":"Proceedings of the National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2017,6,13]]},"abstract":"<jats:title>Significance<\/jats:title>\n          <jats:p>Protein disulfide isomerase (PDI) is a ubiquitous enzyme involved in disulfide bond formation during protein folding. It has been related to neurological diseases (Parkinson or Alzheimer\u2019s) because of unfolded protein response phenomena. It also participates in the regulation of the glutathione redox buffer [glutathione\/glutathione disulfide (GSH\/GSSG)] in the endoplasmic reticulum, also important in protein folding. PDI catalyzes the nucleophilic attack of thiolates to disulfide bonds (thiol-disulfide exchange), enhancing the formation of correct disulfide links that drive protein folding and ensure protein function. This reaction is ubiquitous to disulfide-oxidoreductases across several organisms, and it shows a distinctive chemistry. We present the enzymatic mechanism of PDI in the GSH\/GSSG buffer and discuss the chemistry of thiol-disulfide exchange.<\/jats:p>","DOI":"10.1073\/pnas.1618985114","type":"journal-article","created":{"date-parts":[[2017,5,31]],"date-time":"2017-05-31T00:40:24Z","timestamp":1496191224000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":61,"title":["Mechanistic insights on the reduction of glutathione disulfide by protein disulfide isomerase"],"prefix":"10.1073","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2032-9308","authenticated-orcid":false,"given":"Rui P. P.","family":"Neves","sequence":"first","affiliation":[{"name":"Unidade de Ci\u00eancias Biomoleculares Aplicadas, Rede de Qu\u00edmica e Tecnologia, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2748-4722","authenticated-orcid":false,"given":"Pedro Alexandrino","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Unidade de Ci\u00eancias Biomoleculares Aplicadas, Rede de Qu\u00edmica e Tecnologia, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7554-8324","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Ramos","sequence":"additional","affiliation":[{"name":"Unidade de Ci\u00eancias Biomoleculares Aplicadas, Rede de Qu\u00edmica e Tecnologia, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, 4169-007 Porto, Portugal"}]}],"member":"341","published-online":{"date-parts":[[2017,5,30]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar000063m"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0507985"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm954"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2007.09.003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/1479-7364-6-6"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4439"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)46953-0"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200311055"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.73.011303.074134"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.034"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2013.10.017"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00051a027"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.03.024"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.10.044"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4630"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1997.1504"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/317267a0"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/ct800161m"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1997.t01-1-00037.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2009.06884.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20090565"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.303149"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082511"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2466"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47373-5"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/11047"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.230"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.156596"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806645200"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2014.00070"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2750335"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3151001"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi9617724"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.12.014"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2003.10.051"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2005.06.012"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp806465e"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4521"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(89)90527-5"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi980333x"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2004.01.009"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp0549780"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.200305343"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp7104665"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1021\/ct500840f"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1139\/v83-191"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00532204"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2012.09.018"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00451a013"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.14.8845"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211036200"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi960335m"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi961801a"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400311"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2006.06.001"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2014.00073"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.2560"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1570-9639(04)00063-9"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.39.24992"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2007.03.025"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00191a022"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi960755b"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304951200"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2014.09.001"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1021\/ct100578z"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1021\/ct200133y"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008341820489"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008331225208"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.104.051938"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21123"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.22711"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00124a002"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1002\/1096-987X(200009)21:12<1049::AID-JCC3>3.0.CO;2-F"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1021\/j100142a004"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.445869"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.448118"},{"key":"e_1_3_3_77_2","first-page":"530","article-title":"Sur la th\u00e9orie du mouvement brownien","volume":"146","author":"Langevin P","year":"1908","unstructured":"P Langevin, Sur la th\u00e9orie du mouvement brownien. C R Acad Sci 146, 530\u2013532 (1908).","journal-title":"C R Acad Sci"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9991(77)90098-5"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1002\/andp.19213690304"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540160911"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja9037142"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr400388t"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200802019"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr5004419"},{"key":"e_1_3_3_85_2","first-page":"7:e1281","article-title":"Application of quantum mechanics\/molecular mechanics methods in the study of enzymatic reaction mechanisms","author":"Sousa SF","year":"2017","unstructured":"SF Sousa, , Application of quantum mechanics\/molecular mechanics methods in the study of enzymatic reaction mechanisms. WIREs Comput Mol Sci, pp. 7:e1281 (2017).","journal-title":"WIREs Comput Mol Sci"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-386485-7.00003-X"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi400215w"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2007.03.018"},{"key":"e_1_3_3_89_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr500628b"},{"key":"e_1_3_3_90_2","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.10"},{"key":"e_1_3_3_91_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540070604"},{"key":"e_1_3_3_92_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540110605"},{"key":"e_1_3_3_93_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.1520134"},{"key":"e_1_3_3_94_2","doi-asserted-by":"publisher","DOI":"10.1021\/ct050289g"},{"key":"e_1_3_3_95_2","volume-title":"GAUSSIAN 09, Revision E.01","author":"Frisch MJ","year":"2009","unstructured":"MJ Frisch, GAUSSIAN 09, Revision E.01 (Gaussian, Inc., Wallingford, CT, 2009)."},{"key":"e_1_3_3_96_2","volume-title":"Electronic Density Functional Theory: Recent Progress and New Directions","author":"Burke K","year":"1998","unstructured":"K Burke, JP Perdew, Y Wang Electronic Density Functional Theory: Recent Progress and New Directions (Springer Plenum, New York, 1998)."},{"key":"e_1_3_3_97_2","volume-title":"Electronic Structure of Solids \u201991","author":"Perdew JP","year":"1991","unstructured":"JP Perdew Electronic Structure of Solids \u201991 (Akademie Verlag, Berlin, 1991)."},{"key":"e_1_3_3_98_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevB.54.16533"},{"key":"e_1_3_3_99_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevB.46.6671"},{"key":"e_1_3_3_100_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.475428"},{"key":"e_1_3_3_101_2","doi-asserted-by":"publisher","DOI":"10.1002\/poc.548"},{"key":"e_1_3_3_102_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp021590l"},{"key":"e_1_3_3_103_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp000497z"},{"key":"e_1_3_3_104_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.470829"},{"key":"e_1_3_3_105_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevA.38.3098"},{"key":"e_1_3_3_106_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp049908s"},{"key":"e_1_3_3_107_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp048147q"},{"key":"e_1_3_3_108_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.1589004"},{"key":"e_1_3_3_109_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201200497"},{"key":"e_1_3_3_110_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00088a030"},{"key":"e_1_3_3_111_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200700465"},{"key":"e_1_3_3_112_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.02.037"},{"key":"e_1_3_3_113_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2007.1837"},{"key":"e_1_3_3_114_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20050770"},{"key":"e_1_3_3_115_2","unstructured":"Grossfield A (2013) WHAM: The Weighted Histogram Analysis Method (Department of Biochemistry and Biophysics University of Rochester Medical Center Rochester NY) Version 2.0.9."},{"key":"e_1_3_3_116_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00037a009"},{"key":"e_1_3_3_117_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a123291"},{"key":"e_1_3_3_118_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(98)90005-2"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1618985114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T06:53:19Z","timestamp":1649832799000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1618985114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,30]]},"references-count":118,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2017,6,13]]}},"alternative-id":["10.1073\/pnas.1618985114"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1618985114","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,30]]},"assertion":[{"value":"2017-05-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}