{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:24:15Z","timestamp":1790047455901,"version":"4.0.1"},"reference-count":59,"publisher":"Wiley","issue":"46","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFGRTG2737"],"award-info":[{"award-number":["DFGRTG2737"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFGDE1431\/19\u20101"],"award-info":[{"award-number":["DFGDE1431\/19\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The absence of a universal reducing agent distinguishes the Prx6\u2010type subfamily of peroxiredoxins from the structurally similar Prx1\u2010type subfamily. A likely explanation for the lack of reactivity of Prx6\u2010type enzymes with common reducing agents is that a histidyl residue at the bottom of the active\u2010site pocket traps the oxidized enzyme in an inaccessible fully\u2010folded protein conformation. Here, we analyzed the reduction of oxidized PfPrx6 from\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    and human PrxVI by the hydrosulfide ion, HS\n                    <jats:sup>\u2212<\/jats:sup>\n                    , as the smallest possible sulfur\u2010containing universal electron donor. We show that HS\n                    <jats:sup>\u2212<\/jats:sup>\n                    rapidly reacts with oxidized wild\u2010type PfPrx6 or human PrxVI (but not the histidyl mutants PfPrx6\n                    <jats:sup>H39Y<\/jats:sup>\n                    or hPrxVI\n                    <jats:sup>H39Y<\/jats:sup>\n                    ) with a second\u2010order rate constant of &gt;\u00a010\n                    <jats:sup>8<\/jats:sup>\n                    <jats:sc>m<\/jats:sc>\n                    <jats:sup>\u20121<\/jats:sup>\n                    s\n                    <jats:sup>\u20121<\/jats:sup>\n                    at pH 7.4. The obtained protein\u2010hydropersulfide species is neither reduced by thioredoxin nor glutaredoxin and glutathione, but further reacts with an excess of HS\n                    <jats:sup>\u2212<\/jats:sup>\n                    with a second\u2010order rate constant around 10\n                    <jats:sup>4<\/jats:sup>\n                    <jats:sc>m<\/jats:sc>\n                    <jats:sup>\u20121<\/jats:sup>\n                    s\n                    <jats:sup>\u20121<\/jats:sup>\n                    , yielding the reduced enzyme. In summary, we identified HS\n                    <jats:sup>\u2212<\/jats:sup>\n                    as a highly reactive, potential universal electron donor for Prx6\u2010type enzymes. This study marks the starting point for the characterization of the complex reduction pathway of Prx6\u2010type enzymes with implications for H\n                    <jats:sub>2<\/jats:sub>\n                    S detoxification and redox signaling as well as iron\u2010sulfur and persulfide metabolism.\n                  <\/jats:p>","DOI":"10.1002\/advs.202507214","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T08:22:52Z","timestamp":1759306972000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["H\n                    <sub>2<\/sub>\n                    S Is a Potential Universal Reducing Agent for Prx6\u2010Type Peroxiredoxins"],"prefix":"10.1002","volume":"12","author":[{"given":"Lukas","family":"Lang","sequence":"first","affiliation":[{"name":"Faculty of Chemistry Comparative Biochemistry RPTU Kaiserslautern  D\u201067663 Kaiserslautern Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Leiskau","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry Comparative Biochemistry RPTU Kaiserslautern  D\u201067663 Kaiserslautern Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Bambach","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry Comparative Biochemistry RPTU Kaiserslautern  D\u201067663 Kaiserslautern Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Deponte","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry Comparative Biochemistry RPTU Kaiserslautern  D\u201067663 Kaiserslautern Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.11.6303"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060815-014431"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2002.040"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1080405"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2012.09.018"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7162"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.05.002"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002325"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08565-8"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3624"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406367200"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3490"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2008.04.033"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2011.07.002"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004410050069"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(01)00579-2"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1089\/108076801750125775"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2004.12.008"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005284"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.2c04896"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2006.8.1227"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400181101"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019101552"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2020.06.015"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700481104"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.10.027"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-024-01329-z"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00039.2013"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.03.033"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0598-400"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvp154"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709822105"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2013.07.001"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202203684"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2023.08.005"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201007175"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.008883"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2013.04.020"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45808-9"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103410"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax8358"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1500968"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5SC04818D"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2016.09.018"},{"key":"e_1_2_8_45_1","doi-asserted-by":"crossref","unstructured":"E.Cuevasanta 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