Antony R. Crofts, Sangjin Hong, Charles Wilson, Rodney Burton, Doreen Victoria,
Chris Harrison, and Klaus Schulten.
The mechanism of ubihydroquinone oxidation at the Qo-site of
the cytochrome bc1 complex.
Biochimica et Biophysica Acta, 1827:1362-1377, 2013.
(PMC: PMC3995752)
CROF2013
1. Recent results suggest that the major flux is carried by a monomeric function, not by
an
intermonomer electron flow. 2. The bifurcated reaction at the Q-site involves
sequential partial processes, - a rate limiting first electron transfer generating a
semiquinone (SQ) intermediate, and a rapid second electron transfer in which the SQ is
oxidized by the low potential chain. 3. The rate constant for the first step in a strongly
end-ergonic, proton-first-then-electron mechanism, is given by a Marcus–Br
treatment in which a rapid electron transfer is convoluted with a weak occupancy of the
proton configuration needed for electron transfer. 4. A rapid second electron transfer
pulls
the overall reaction over. Mutation of Glu-295 of cyt b shows it to be a key player.
5.
In more crippled mutants, electron transfer is severely inhibited and the bell-shaped pH
dependence of wildtype is replaced by a dependence on a single pK at 8.5
favoring
electron transfer. Loss of a pK 6.5 is explained by a change in the rate limiting
step
from the first to the second electron transfer; the pK 8.5 may reflect dissociation
of
QH. 6. A rate constant (s) for oxidation of SQ in the
distal
domain by heme has been determined, which precludes mechanisms for
normal flux in which SQ is constrained there. 7. Glu-295 catalyzes proton exit through
H transfer from QH, and rotational displacement to deliver the H to
exit channel(s). This opens a volume into which Q - can move closer to the
heme to speed electron transfer. 8. A kinetic model accounts well for the observations,
but
leaves open the question of gating mechanisms. For the first step we suggest a
molecular
“escapement”; for the second a molecular ballet choreographed through coulombic
interactions.
This article is part of a Special Issue entitled: Respiratory complex III and related bc
complexes.
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