title: RETRACTED: Protonation State-Dependent Communication in Cytochrome c Oxidase.
abstract: Proton transfer in cytochrome c oxidase from the cellular inside to the binuclear redox center (BNC) can occur through two distinct pathways, the D- and K-channels. For the protein to function as both redox enzyme and proton pump, proton transfer out of either of the channels toward the BNC or into the protein toward a proton loading site, and ultimately through the membrane, must be highly regulated. The O→E intermediate of cytochrome c oxidase is the first redox state in its catalytic cycle, where proton transfer through the K-channel, from K362 to Y288 at the BNC, is important. Molecular dynamics simulations of this intermediate with 16 different combinations of protonation states of key residues in the D- and K-channel show the mutual impact of the two proton-conducting channels to be protonation state-dependent. Strength as well as means of communication, correlations in positions, or connections along the hydrogen-bonded network, change with the protonation state of the K-channel residue K362. The conformational and hydrogen-bond dynamics of the D-channel residue N139 regulated by an interplay of protonation in the D-channel and K362. N139 thus assumes a gating function by which proton passage through the D-channel toward E286 is likely facilitated for states with protonated K362 and unprotonated E286, which would in principle allow proton transfer to the BNC, but no proton pumping until a proton has reached E286.
authors: Institute of Theoretical Physics, Free University Berlin, Berlin, Germany.
authors: Mahdi Bagherpoor
authors: MB
authors: Helabad
authors: Institute of Theoretical Physics, Free University Berlin, Berlin, Germany.
authors: Tahereh
authors: T
authors: Ghane
authors: Institute of Theoretical Physics, Free University Berlin, Berlin, Germany.
authors: Marco
authors: M
authors: Reidelbach
authors: Institute of Pharmacy, Free University Berlin, Berlin, Germany.
authors: Anna Lena
authors: AL
authors: Woelke
authors: Institute of Biochemistry, Free University Berlin, Berlin, Germany.
authors: Ernst Walter
authors: EW
authors: Knapp
authors: Institute of Theoretical Physics, Free University Berlin, Berlin, Germany. Electronic address: pimhof@zedat.fu-berlin.de.
authors: Petra
authors: P
authors: Imhof
mesh_terms: D003576:Electron Transport Complex IV / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D011522:Protons
chemical_list: D011522:Protons; D003576:Electron Transport Complex IV