Format

Send to

Choose Destination
See comment in PubMed Commons below
FEBS Lett. 2005 Apr 11;579(10):2026-34.

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

Author information

1
Department of Chemistry, University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089-1062, USA. molsson@usc.edu

Abstract

Gaining a detailed understanding of the molecular nature of the redox coupled proton transfer in cytochrome c oxidase (COX) is one of the challenges of modern biophysics. The present work addresses this by integrating approaches for simulations of proton transport (PTR) and electron transfer (ET). The resulting method converts the electrostatic energies of different charge configurations and reorganization energies to free-energy profiles for different PTR and ET pathways. This approach provides for the first time a tool to study the actual activation barriers and kinetics of different feasible PTR processes in the cycle of COX. Using this tool, we explore the PTR through the bottleneck water molecules. It is found that a stepwise PTR along this commonly assumed path leads to far too high barriers and is, thus, inconsistent with the observed kinetics. Furthermore, the simulated free-energy profile does not provide a simple gating mechanism. Fortunately, we obtain reasonable kinetics when we consider a PTR that involves a concerted transfer of protons to and from E286. Finally, semi-qualitative considerations of the forward and backward barriers point toward open questions about the actual gating process and offer a feasible pumping mechanism. Although further studies are clearly needed, we believe that our approach offers a general and effective tool for correlating the structure of COX with its function.

PMID:
15811313
DOI:
10.1016/j.febslet.2005.02.051
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Support Center