{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T12:02:07Z","timestamp":1778587327299,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T00:00:00Z","timestamp":1649462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DE 1431\/8\u20102"],"award-info":[{"award-number":["DE 1431\/8\u20102"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Peroxiredoxins use a variety of thiols to rapidly reduce hydroperoxides and peroxynitrite. While the oxidation kinetics of peroxiredoxins have been studied in great detail, enzyme\u2010specific differences regarding peroxiredoxin reduction and the overall rate\u2010limiting step under physiological conditions often remain to be deciphered. The 1\u2010Cys peroxiredoxin 5 homolog PfAOP from the malaria parasite <jats:italic>Plasmodium falciparum<\/jats:italic> is an established model enzyme for glutathione\/glutaredoxin\u2010dependent peroxiredoxins. Here, we reconstituted the catalytic cycle of PfAOP <jats:italic>in vitro<\/jats:italic> and analyzed the reaction between oxidized PfAOP and reduced glutathione (GSH) using molecular docking and stopped\u2010flow measurements. Molecular docking revealed that oxidized PfAOP has to adopt a locally unfolded conformation to react with GSH. Furthermore, we determined a second\u2010order rate constant of 6\u2009\u00d7\u200910<jats:sup>5<\/jats:sup>\u2009M<jats:sup>\u22121<\/jats:sup>\u00a0s<jats:sup>\u22121<\/jats:sup> at 25\u00b0C and thermodynamic activation parameters \u0394<jats:italic>H<\/jats:italic><jats:sup>\u2021<\/jats:sup>, \u0394<jats:italic>S<\/jats:italic><jats:sup>\u2021<\/jats:sup>, and \u0394<jats:italic>G<\/jats:italic><jats:sup>\u2021<\/jats:sup> of 39.8\u00a0kJ\/mol, \u22120.8\u00a0J\/mol, and 40.0\u00a0kJ\/mol, respectively. The gain\u2010of\u2010function mutant PfAOP<jats:sup>L109M<\/jats:sup> had almost identical reaction parameters. Taking into account physiological hydroperoxide and GSH concentrations, we suggest (a) that the reaction between oxidized PfAOP and GSH might be even faster than the formation of the sulfenic acid <jats:italic>in vivo<\/jats:italic>, and (b) that conformational changes are likely rate limiting for PfAOP catalysis. In summary, we characterized and quantified the reaction between GSH and the model enzyme PfAOP, thus providing detailed insights regarding the reactivity of its sulfenic acid and the versatile chemistry of peroxiredoxins.<\/jats:p>","DOI":"10.1002\/pro.4290","type":"journal-article","created":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T14:56:49Z","timestamp":1649516209000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Characterization of the glutathione\u2010dependent reduction of the peroxiredoxin 5 homolog <scp>PfAOP<\/scp> from <i>Plasmodium falciparum<\/i>"],"prefix":"10.1002","volume":"31","author":[{"given":"Robin","family":"Schumann","sequence":"first","affiliation":[{"name":"Faculty of Chemistry TU Kaiserslautern  Kaiserslautern Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"Lang","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry TU Kaiserslautern  Kaiserslautern Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2141-917X","authenticated-orcid":false,"given":"Marcel","family":"Deponte","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry TU Kaiserslautern  Kaiserslautern 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