RETRACTED: Protonation State-Dependent Communication in Cytochrome c Oxidase.

Area of Science:

• Biochemistry
• Molecular Biology
• Biophysics

Background:

• Cytochrome c oxidase is a crucial enzyme functioning as both a redox enzyme and a proton pump.
• Proton transfer occurs via two distinct pathways: the D-channel and the K-channel, leading to the binuclear redox center (BNC).
• Efficient proton transfer regulation is essential for the enzyme's dual function.

Purpose of the Study:

• To investigate the protonation state-dependent interplay between the D- and K-channels in cytochrome c oxidase.
• To understand how residue protonation influences proton transfer pathways and communication within the enzyme.
• To elucidate the gating mechanism of the D-channel residue N139.

Main Methods:

• Utilized molecular dynamics simulations.
• Examined 16 different combinations of protonation states for key residues in the D- and K-channels.
• Analyzed the O→E intermediate of cytochrome c oxidase.

Main Results:

• The mutual impact of the D- and K-channels is significantly dependent on the protonation states of their residues.
• The protonation state of K362 in the K-channel alters the communication strength and pathways within the hydrogen-bonded network.
• N139 in the D-channel exhibits gating behavior, influenced by D-channel and K362 protonation, facilitating proton transfer to E286 under specific conditions.

Conclusions:

• Proton transfer pathways in cytochrome c oxidase are dynamically regulated by the protonation states of key channel residues.
• The D-channel residue N139 acts as a gate, controlling proton flow towards the binuclear redox center.
• Understanding these protonation-dependent dynamics is key to comprehending the enzyme's function as a proton pump.