Structural elements involved in electron-coupled proton transfer in cytochrome c oxidase

Abstract

Haem-copper oxidases are the last components of the respiratory chains in aerobic organisms. These membrane-bound enzymes energetically couple the electron transfer (eT) reactions associated with reduction of dioxygen to water, to proton pumping across the membrane. Even though the mechanism of proton pumping at the molecular level still remains to be uncovered, recent progress has presented us with the structural features of the pumping machinery and detailed information about the eT and proton-transfer reactions associated with the pumping process.

Simulating redox coupled proton transfer in cytochrome c oxidase: Looking for the proton bottleneck

“…Despite the above arguments it is clear that we have not explored the possibility [7,13] that conformational changes contribute to the gating mechanism. Now, although this mechanism, by itself, cannot be established (or eliminated) without evaluating the structures of different conformational states, the present study indicates that such changes might not explain the pumping process.…”

“…However, the actual energetics of the PTR process was not examined. The nature of the gating mechanism was also discussed by Namslauer and Brzezinski [13], who proposed a mechanism that couples conformational changes and p K a changes. This mechanism considered a transient reduction in the p K a value of E286 coupled with an increase in the p K a value of a group on the P side and conformational changes that lead to a change in the hydrogen bonding connectivity and helps in providing a gating process.…”

“…The origin of the gating mechanism in COX has been the subject of significant recent interest [7,8,12,13] but none of the recent studies have evaluated the actual barriers for the PTR process. For example, Wikstrom et al [8], who considered the orientation of the water molecules in the hydrophobic region between heme a and heme a3, have raised the important issue of the gating mechanism.…”

“…For example, some workers, e.g. [13], favors PTR to the iron‐bound oxygen before the PTR to Prd. Nevertheless, Fig.…”

“…The nature of the pumping process was eloquently considered by Mills and Ferguson‐Miller [12] who assessed the evidences for direct and indirect coupling mechanism, where the indirect mechanism involves conformational and p K a changes. The details of a conformational mechanism have been considered by Brzezinski and coworkers [7,13]. Although this proposal has appealing aspects, it cannot be verified without specific tools of converting structures to p K a values.…”