Choreography of the Qo-site to minimize bypass reactions

The animation shows the sequence of reactions at the Qo-site on oxidation of the ubiquinone pool under conditions in which the bc1 complex is inhibited by antimycin. The main players at the Qo-site are shown, together with the two b-hemes, with heme bL adjacent to the site.
  1. The first turnover of the site leads to reduction of heme bH.
  2. The second turnover leads to the reduction of heme bL.
  3. The third turnover is truncated after the first electron transfer fron QH2 because there is no acceptor available for the electron from the semiquinone (SQ) generated in that partial reaction.
In the mechanism suggested (1, 2), the second electron transfer of the bifurcated reaction, from SQ to heme bL, requires movement of the liganding glutamate (Glu-295 in Rhodobacter sphaeroides) in its acidic form to carry the second proton out of the site by dissociation of the H+ to the water chain shown. This liberates the semiquinone anion (Q.-), which can then move to the proximal domain of the site to deliver its electron to heme bL. This movement lowers the distance for electron transfer so as to increase the rate constant by a factor of ~103. As a consequence, the local concentration of SQ can be kept much lower, thus minimizing the possibility of short-circuits by electron donation to O2 or ISPox.
Osyczka et al. (3) noted that any mechanism requiring a SQ intermediate in the Qo-site reaction would suffer from a potential bypass through reduction of SQ by reduced heme bL, because the rate constant for this reaction would be similar to that for the forward electron transfer fron SQ to oxidized heme bL. They pointed out the need for some gating mechanism.
In the context of the mechanism above, we can minimize this bypass reaction, by preventing SQ from getting close to the reduced heme bL. Crofts et al. (4) suggested that this would be achieved by coulombic repulsion between the reduced heme and the Q.-, which thus provides a coulombic gating.
Although the oxidized heme formally carries a +ve charge, and the reduced heme would be neutral, the charges in situ will be determined by the local electrostatics of the protein. The important point is that the reduced heme-binding site will carry a net -ve charge compared to the oxidized state.


  1. Crofts, A.R., Barquera, B., Gennis, R.B., Kuras, R., Guergova-Kuras, M. and Berry, E.A. (1999) The mechanism of ubiquinol oxidation by the bc1 complex: the different domains of the quinol binding pocket, and their role in mechanism, and the binding of inhibitors. Biochemistry 38, 15807-15826. Reprint

  2. Crofts, A.R., Hong, S.J., Ugulava, N., Barquera, B., Gennis, R.B., Guergova-Kuras, M., and Berry, E. (1999) Pathways for proton release during ubihydroquinone oxidation by the bc1 complex. Proc. Natl. Acad. Sci. U.S.A., 96, 10021-10026. Reprint (PDF format)

  3. Osyczka, A., Moser, C.C., Daldal, F. and Dutton, P.L. (2004) Reversible redox energy coupling in electron transfer chains, Nature 427, 607612.

  4. Crofts, A.R., Lhee, S., Crofts, S.B., Cheng, J. and Rose, S. (2006) Proton pumping in the bc1 complex: A new gating mechanism that prevents short circuits. Biochim. Biophys. Acta, 1757, 1019-1034. Reprint