Interview for Faculty Position

Cytochrome c Oxidase: The biological fuel cell

Youngchan Kim

Laboratory of Chemical Physics
National Institute of Diabetes and Digestive and Kidney Diseases

Cytochrome c oxidase (CcO) is the main energy transducer in aerobic life. CcO catalyzes the reduction of oxygen to water, a reaction equivalent to hydrogen fuel cell. The energy released in this exergonic reaction is stored in an electric potential across a membrane. Remarkably, CcO appears to act like a Maxwells Demon by pumping protons from one side of the membrane to the other. Understanding the fundamental mechanism of this proton-pumping process has been a challenging issue in the biophysics and biochemistry for more than 30 years since its discovery in 1977. To explore the fundamental mechanism of this molecular machine, we develop coarse-grained kinetic models at the single-molecule level consistent with basic physical principles and the structure of CcO. Using the Monte Carlo optimization of the models in the parameter space, we show that the three-site model with two proton sites and one electron site can pump protons via electrostatic interactions. Furthermore, we show that the internal proton transfer should be tightly coupled to the electron uptake in order to have high proton-pumping efficiency. The three-site model produces quantitatively all the available experimental thermodynamic and kinetic data of CcO. This study provides general design principles for other molecular machines and biology-inspired fuel cells.