Gating of proton and water transfer in the respiratory enzyme cytochrome c oxidase
AUTOR(ES)
Wikström, Mårten
FONTE
National Academy of Sciences
RESUMO
The membrane-bound enzyme cytochrome c oxidase is responsible for cell respiration in aerobic organisms and conserves free energy from O2 reduction into an electrochemical proton gradient by coupling the redox reaction to proton-pumping across the membrane. O2 reduction produces water at the bimetallic heme a3/CuB active site next to a hydrophobic cavity deep within the membrane. Water molecules in this cavity have been suggested to play an important role in the proton-pumping mechanism. Here, we show by molecular dynamics simulations that the conserved arginine/heme a3 Δ-propionate ion pair provides a gate, which exhibits reversible thermal opening that is governed by the redox state and the water molecules in the cavity. An important role of this gate in the proton-pumping mechanism is supported by site-directed mutagenesis experiments. Transport of the product water out of the enzyme must be rigidly controlled to prevent water-mediated proton leaks that could compromise the proton-pumping function. Exit of product water is observed through the same arginine/propionate gate, which provides an explanation for the observed extraordinary spatial specificity of water expulsion from the enzyme.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1180778Documentos Relacionados
- Proton uptake controls electron transfer in cytochrome c oxidase
- On the role of the K-proton transfer pathway in cytochrome c oxidase
- Kinetic coupling between electron and proton transfer in cytochrome c oxidase: simultaneous measurements of conductance and absorbance changes.
- The mechanism of proton pumping by cytochrome c oxidase
- Possible proton relay pathways in cytochrome c oxidase.