{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T14:38:46Z","timestamp":1768315126471,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:00:00Z","timestamp":1755907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:00:00Z","timestamp":1755907200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["PID2019\u2010110900GB\u2010I00"],"award-info":[{"award-number":["PID2019\u2010110900GB\u2010I00"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["PID2022\u2010136307OB\u2010C22"],"award-info":[{"award-number":["PID2022\u2010136307OB\u2010C22"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["PID2022\u2010136369NB\u2010I00"],"award-info":[{"award-number":["PID2022\u2010136369NB\u2010I00"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["PID2023\u2010150714OB\u2010I00"],"award-info":[{"award-number":["PID2023\u2010150714OB\u2010I00"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Ferredoxin\u2010dependent flavin thioredoxin reductases (FFTRs) catalyze the reduction of the disulfide bond in thioredoxins using electrons transferred from ferredoxin, and therefore play a pivotal role in cellular disulfide relay reactions. FFTRs are essential in cyanobacteria such as\n                    <jats:italic>Gloeobacter<\/jats:italic>\n                    and\n                    <jats:italic>Prochlorococcus<\/jats:italic>\n                    , in which they serve as the sole thioredoxin reduction system, as well as in certain\n                    <jats:italic>Clostridium<\/jats:italic>\n                    species, where they are implicated in processes such as sporulation. Despite the well\u2010established role of ferredoxin in reducing FFTRs, the underlying mechanistic details remain poorly understood. This study examines the catalytic cycle of FFTR from\n                    <jats:italic>Gloeobacter violaceus<\/jats:italic>\n                    , focusing on the role of its redox\u2010active disulfide in electron transfer. We demonstrate that FFTR has a highly negative flavin adenine dinucleotide (FAD) midpoint reduction potential, which explains its preference for ferredoxin over nicotinamide adenine dinucleotide phosphate (NADPH) as an electron source. Spectroscopic detection of a thiolate\u2013flavin charge transfer complex along the enzyme reduction pathway provides the first experimental evidence of a previously elusive FFTR catalytic conformation. Our results further reveal sequential FAD reduction within the enzyme homodimer that strongly suggests monomer asymmetry. Moreover, the impaired flavin reduction observed in an enzyme variant lacking the disulfide highlights the essential role of this redox group in efficient electron transfer. These findings deepen our understanding of FFTR's unique functional adaptations and evolutionary significance. More broadly, they provide a framework for exploring similar electron transfer mechanisms in other flavoproteins with a view to expanding our understanding of their redox biochemistry.\n                  <\/jats:p>","DOI":"10.1111\/febs.70210","type":"journal-article","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T07:06:53Z","timestamp":1755932813000},"page":"96-112","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanism of cyanobacterial ferredoxin\u2010dependent flavin thioredoxin reductase reveals thiolate\u2010\n                    <scp>FAD<\/scp>\n                    charge transfer and catalytic asymmetry in a homodimer"],"prefix":"10.1111","volume":"293","author":[{"given":"Martha","family":"Minjarez\u2010Saenz","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular and Cellular Biology, Faculty of Sciences and Institute for Biocomputation and Physics of Complex Systems (BIFI) University of Zaragoza  Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00edctor","family":"Correa\u2010P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular and Cellular Biology, Faculty of Sciences and Institute for Biocomputation and Physics of Complex Systems (BIFI) University of Zaragoza  Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maribel","family":"Rivero","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular and Cellular Biology, Faculty of Sciences and Institute for Biocomputation and Physics of Complex Systems (BIFI) University of Zaragoza  Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Hern\u00e1ndez\u2010G\u00f3mez","sequence":"additional","affiliation":[{"name":"Department of Abiotic Stress Institute of Natural Resources and Agrobiology of Salamanca (IRNASA\u2010CSIC)  Spain"},{"name":"Metabolic Engineering Group, Department of Genetic and Microbiology, Faculty of Biology University of Salamanca  Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9047-0046","authenticated-orcid":false,"given":"Marta","family":"Mart\u00ednez\u2010J\u00falvez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular and Cellular Biology, Faculty of Sciences and Institute for Biocomputation and Physics of Complex Systems (BIFI) University of Zaragoza  Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rub\u00e9n M.","family":"Buey","sequence":"additional","affiliation":[{"name":"Metabolic Engineering Group, Department of Genetic and Microbiology, Faculty of Biology University of Salamanca  Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Gago","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine and Health Sciences University of Alcal\u00e1  Alcal\u00e1 de Henares Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5586-6050","authenticated-orcid":false,"given":"Monica","family":"Balsera","sequence":"additional","affiliation":[{"name":"Department of Abiotic Stress Institute of Natural Resources and Agrobiology of Salamanca (IRNASA\u2010CSIC)  Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8743-0182","authenticated-orcid":false,"given":"Milagros","family":"Medina","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular and Cellular Biology, Faculty of Sciences and Institute for Biocomputation and Physics of Complex Systems (BIFI) University of Zaragoza  Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.07.036"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2007.1931"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.03.003"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molp.2016.06.019"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/plphys\/kiab072"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.12.3681"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1812781115"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1012001"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01702.x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.1190"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5482.1190"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2010.06.024"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560061013"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)93272-2"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi200107n"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.8.3621"},{"key":"e_1_2_10_18_1","first-page":"59","volume-title":"Flavins and Flavoproteins","author":"Massey V","year":"1990"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mie.2019.03.004"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)74022-8"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40297-8"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi952521i"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mie.2019.03.005"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(95)52023-6"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07487-w"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05937"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.3c00051"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9090772"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4957"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.3c00042"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2007.10.034"},{"key":"e_1_2_10_32_1","first-page":"1","article-title":"UV\u2010visible spectroscopy as a tool to study flavoproteins","volume":"131","author":"Macheroux P","year":"1999","journal-title":"Methods Mol Biol"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)40065-2"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.3571"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20161089"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2013.12.030"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-1286-6_9"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi049858h"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.70210","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/febs.70210","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.70210","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T09:14:36Z","timestamp":1768295676000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.70210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,23]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/febs.70210"],"URL":"https:\/\/doi.org\/10.1111\/febs.70210","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,23]]},"assertion":[{"value":"2025-04-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}