TY  - JOUR
A1  - Herzog, Elena
A1  - Gu, Wei
A1  - Juhnke, Hanno Dominik
A1  - Haas, Alexander H.
A1  - Mäntele, Werner
A1  - Simon, Jörg
A1  - Helms, Volkhard
A1  - Lancaster, C. Roy D.
T1  - Hydrogen-bonded networks along and bifurcation of the E-pathway in quinol:fumarate reductase
T2  - Biophysical journal : BJ
N2  - 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.
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/28881
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-288817
SN  - 0006-3495
SN  - 1542-0086
N1  - 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.
VL  - 103
IS  - 6
SP  - 1305
EP  - 1314
PB  - Biophysical Soc. [u.a.]
CY  - Bethesda, Md.
ER  -