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C\n                    <jats:italic>c<\/jats:italic>\n                    O can slow the formation of reactive oxygen species and is key to physiology and drug development. The exact molecular mechanisms underlying its proton\u2010pumping function remain elusive. The redox state of C\n                    <jats:italic>c<\/jats:italic>\n                    O's metallic cofactors is intimately connected to structural changes and proton pumping via proton\u2010coupled electron transfer. Time\u2010resolved UV\/Vis and IR spectroscopy are used to investigate the effects of the electronic backreaction triggered by photolyzing the CO\u2010inhibited 2\u2010electron reduced state,\n                    <jats:bold>R<\/jats:bold>\n                    <jats:sub>\n                      <jats:bold>2<\/jats:bold>\n                    <\/jats:sub>\n                    <jats:bold>CO<\/jats:bold>\n                    , in the\n                    <jats:italic>aa<\/jats:italic>\n                    <jats:sub>3<\/jats:sub>\n                    oxidase from\n                    <jats:italic>Cereibacter sphaeroides<\/jats:italic>\n                    . An intermediate is identified, in which the binuclear center matches the redox state of the catalytic intermediate\n                    <jats:bold>E<\/jats:bold>\n                    (one\u2010electron reduced state), with a rise time of \u22482\u2009\u03bcs. The electron transfer induces structural changes that lead to E286 deprotonation, with a time constant of 13\u2009\u03bcs. Thus, it is inferred that transient reduction of heme\n                    <jats:italic>a<\/jats:italic>\n                    alone drives E286 deprotonation. E286 is reprotonated with a time constant of 72\u2009ms when CO rebinds. The results support the view that transient heme\n                    <jats:italic>a<\/jats:italic>\n                    reduction in the physiological\n                    <jats:bold>E<\/jats:bold>\n                    state modulates the electrostatic environment, triggering proton transfer toward the proton\u2010loading site.\n                  <\/jats:p>","DOI":"10.1002\/cphc.202500539","type":"journal-article","created":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T08:55:16Z","timestamp":1762592116000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Proton\u2010Coupled Electron Transfer in Cytochrome\n                    <i>c<\/i>\n                    Oxidase: Heme\n                    <i>a<\/i>\n                    Controls the Protonation Dynamics of E286"],"prefix":"10.1002","volume":"26","author":[{"given":"Federico","family":"Baserga","sequence":"first","affiliation":[{"name":"Department of Physics 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