Hydrogen-bonded networks along and bifurcation of the E-pathway in quinol:fumarate reductase

The E-pathway of transmembrane proton transfer has been demonstrated previously to be essential for catalysis by the diheme-containing quinol:fumarate reductase (QFR) of Wolinella succinogenes. Two constituents of this p
The E-pathway of transmembrane proton transfer has been demonstrated previously to be essential for catalysis by the diheme-containing quinol:fumarate reductase (QFR) of Wolinella succinogenes. Two constituents of this pathway, Glu-C180 and heme b(D) ring C (b(D)-C-) propionate, have been validated experimentally. Here, we identify further constituents of the E-pathway by analysis of molecular dynamics simulations. The redox state of heme groups has a crucial effect on the connectivity patterns of mobile internal water molecules that can transiently support proton transfer from the b(D)-C-propionate to Glu-C180. The short H-bonding paths formed in the reduced states can lead to high proton conduction rates and thus provide a plausible explanation for the required opening of the E-pathway in reduced QFR. We found evidence that the b(D)-C-propionate group is the previously postulated branching point connecting proton transfer to the E-pathway from the quinol-oxidation site via interactions with the heme b(D) ligand His-C44. An essential functional role of His-C44 is supported experimentally by site-directed mutagenesis resulting in its replacement with Glu. Although the H44E variant enzyme retains both heme groups, it is unable to catalyze quinol oxidation. All results obtained are relevant to the QFR enzymes from the human pathogens Campylobacter jejuni and Helicobacter pylori.
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Author:Elena Herzog, Wei Gu, Hanno Dominik Juhnke, Alexander H. Haas, Werner Mäntele, Jörg Simon, Volkhard Helms, C. Roy D. Lancaster
URN:urn:nbn:de:hebis:30:3-288817
DOI:http://dx.doi.org/10.1016/j.bpj.2012.07.037
ISSN:0006-3495
ISSN:1542-0086
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=22995503
Parent Title (English):Biophysical journal : BJ
Publisher:Biophysical Soc. [u.a.]
Place of publication:Bethesda, Md.
Document Type:Article
Language:English
Date of Publication (online):2012/09/19
Date of first Publication:2012/09/19
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2013/02/14
Volume:103
Issue:6
Pagenumber:10
First Page:1305
Last Page:1314
Note:
This is an Open Access article distributed under the terms of the Creative Commons-Attribution Noncommercial License (http://creativecommons. org/licenses/by-nc/2.0/), which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
HeBIS PPN:331532441
Institutes:Biowissenschaften
Dewey Decimal Classification:570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 3.0

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