The identity of the transient proton loading site of the proton-pumping mechanism of cytochrome c oxidase
Tutkimustuotos › › vertaisarvioitu
|Julkaisu||Biochimica et Biophysica Acta: Bioenergetics|
|DOI - pysyväislinkit|
|Tila||Julkaistu - tammikuuta 2011|
Cellular respiration is driven by cytochrome c oxidase (CcO), which reduces oxygen to water and couples the released energy to proton pumping across the mitochondrial or bacterial membrane. Proton pumping in CcO involves proton transfer from the negatively charged side of the membrane to a transient proton-loading or pump site (PLS), before it is ejected to the opposite side. Although many details of the reaction mechanism are known, the exact location of the PLS has remained elusive. We report here results from combined classical molecular dynamics simulations and continuum electrostatic calculations, which show that the hydrogen-bonded system around the A-propionate of heme a3 dissociates reversibly upon reduction of heme a. The dissociation increases the pKa value of the propionate to a value above ~9, making it accessible for redox-state dependent protonation. The redox state of heme a is of key importance in controlling proton leaks by polarizing the PLS both statically and dynamically. These findings suggest that the propionate region of heme a3 fulfills the criteria of the pump site in the proton translocation mechanism of CcO.