TY - JOUR
T1 - The mechanism of ubihydroquinone oxidation at the Qo-site of the cytochrome bc1 complex
AU - Crofts, Antony R.
AU - Hong, Sangjin
AU - Wilson, Charles
AU - Burton, Rodney
AU - Victoria, Doreen
AU - Harrison, Chris
AU - Schulten, Klaus
N1 - Funding Information:
ARC thanks NIH for the support through grant RO1 GM035438 , RB and SH thank Dr. Sergei Dikanov for the support under NIH RO1 GM062954 , KS and CH acknowledge support through NIH PHS 9 P41 GM104601 and NSF PHY0822613 , and CW thanks the Center for Biophysics and Computational Biology for the support through a Research Assistantship for Summer 2012 .
PY - 2013
Y1 - 2013
N2 - 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 Qo-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 endergonic, proton-first-then-electron mechanism, is given by a Marcus-Brønsted 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 (< 103 s- 1) for oxidation of SQ in the distal domain by heme bL 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.
AB - 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 Qo-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 endergonic, proton-first-then-electron mechanism, is given by a Marcus-Brønsted 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 (< 103 s- 1) for oxidation of SQ in the distal domain by heme bL 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.
KW - Bifurcated reaction of Q-cycle
KW - Control and gating
KW - H exit pathway
KW - Kinetic model
KW - Semiquinone occupancy
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U2 - 10.1016/j.bbabio.2013.01.009
DO - 10.1016/j.bbabio.2013.01.009
M3 - Review article
C2 - 23396004
AN - SCOPUS:84884670263
SN - 0005-2728
VL - 1827
SP - 1362
EP - 1377
JO - Biochimica et Biophysica Acta - Bioenergetics
JF - Biochimica et Biophysica Acta - Bioenergetics
IS - 11-12
ER -