Dynamic water networks in cytochrome cbb3 oxidase

Vivek Sharma, Mårten Wikström, Ville R.I. Kaila

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Heme-copper oxidases (HCOs) are terminal electron acceptors in aerobic respiration. They catalyze the reduction of molecular oxygen to water with concurrent pumping of protons across the mitochondrial and bacterial membranes. Protons required for oxygen reduction chemistry and pumping are transferred through proton uptake channels. Recently, the crystal structure of the first C-type member of the HCO superfamily was resolved [Buschmann et al. Science 329 (2010) 327-330], but crystallographic water molecules could not be identified. Here we have used molecular dynamics (MD) simulations, continuum electrostatic approaches, and quantum chemical cluster calculations to identify proton transfer pathways in cytochrome cbb3. In MD simulations we observe formation of stable water chains that connect the highly conserved Glu323 residue on the proximal side of heme b3 both with the N- and the P-sides of the membrane. We propose that such pathways could be utilized for redox-coupled proton pumping in the C-type oxidases. Electrostatics and quantum chemical calculations suggest an increased proton affinity of Glu323 upon reduction of high-spin heme b3. Protonation of Glu323 provides a mechanism to tune the redox potential of heme b3 with possible implications for proton pumping.

Original languageEnglish
Pages (from-to)726-734
Number of pages9
JournalBBA - Bioenergetics
Volume1817
Issue number5
DOIs
StatePublished - May 2012
Externally publishedYes

Keywords

  • Continuum electrostatics
  • Density functional theory (DFT)
  • Molecular dynamics (MD) simulation
  • Proton channel
  • Proton pumping
  • cbb-type cytochrome c oxidase

Fingerprint

Dive into the research topics of 'Dynamic water networks in cytochrome cbb3 oxidase'. Together they form a unique fingerprint.

Cite this