Thermodynamic and choreographic constraints for energy transduction by cytochrome c oxidase.

Cooperative effects are fundamental for electroprotonic energy transduction processes, crucial to sustain much of life chemistry. However, the primary cooperative mechanism by which transmembrane proteins couple the downhill transfer of electrons to the uphill activation (acidification) of protic groups is still a matter of great controversy. To understand cooperative processes fully, it is necessary to obtain the microscopic thermodynamic parameters of the functional centres and relate them to the relevant structural features, a task difficult to achieve for large proteins. The approach discussed here explores how this may be done by extrapolation from mechanisms used by simpler proteins operative in similar processes. The detailed study of small, soluble cytochromes performing electroprotonic activation has shown how they use anti-electrostatic effects to control the synchronous movement of charges. These include negative e(-)/H(+) (redox-Bohr effect) cooperativities. This capacity is the basis to discuss an unorthodox mechanism consistent with the available experimental data on the process of electroprotonic energy transduction performed by cytochrome c oxidase (CcO).