title: Recent progress on obtaining theoretical and experimental support for the "E-pathway hypothesis" of coupled transmembrane electron and proton transfer in dihaem-containing quinol:fumarate reductase.
abstract: Reconciliation of apparently contradictory experimental results obtained on the quinol: fumarate reductase (QFR), a dihaem-containing respiratory membrane protein complex from Wolinella succinogenes, was previously obtained by the proposal of the so-called E-pathway hypothesis. According to this hypothesis, transmembrane electron transfer via the haem groups is strictly coupled to co-transfer of protons via a transiently established, novel pathway, proposed to contain the side chain of residue Glu-C180 and the distal haem ring-C propionate as the most prominent components. This hypothesis has recently been supported by both theoretical and experimental results. Multiconformation continuum electrostatics calculations predict Glu-C180 to undergo a combination of proton uptake and conformational change upon haem reduction. Strong experimental support for the proposed role of Glu-C180 in the context of the "E-pathway hypothesis" is provided by the effects of replacing Glu-C180 with Gln or Ile by site-directed mutagenesis, the consequences of these mutations for the viability of the resulting mutants, together with the structural and functional characterisation of the corresponding variant enzymes, and the comparison of redox-induced Fourier-transform infrared (FTIR) difference spectra for the wild type and Glu-C180-->Gln variant. A possible haem propionate involvement has recently been supported by combining (13)C-haem propionate labelling with redox-induced FTIR difference spectroscopy.
authors.affiliation: Max Planck Institute of Biophysics, Department of Molecular Membrane Biology, Max-Von-Laue-Str 3, Frankfurt am Main, Germany. Roy.Lancaster@mpibp-frankfurt.mpg.de
authors.forename: C Roy D
authors.initials: CR
authors.lastname: Lancaster
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Haas
authors.forename: M Gregor
authors.initials: MG
authors.lastname: Madej
authors.forename: Mauro
authors.initials: M
authors.lastname: Mileni
mesh_terms: D002462:Cell Membrane / Q000502:physiology*; D004579:Electron Transport; D004583:Electrons; D018698:Glutamic Acid; D008954:Models, Biological; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D011522:Protons; D016968:Wolinella / Q000201:enzymology
chemical_list: D011522:Protons; D018698:Glutamic Acid; D010088:Oxidoreductases; C424907:quinol fumarate reductase