Ubiquinol oxidation in the cytochrome bc1 complex: reaction mechanism and prevention of short-circuiting.
This review is focused on the mechanism of ubiquinol oxidation by the cytochrome bc1 complex (bc1). This integral membrane complex serves as a "hub" in the vast majority of electron transfer chains. The bc1 oxidizes a ubiquinol molecule to ubiquinone by a unique "bifurcated" reaction where the two released electrons go to different acceptors: one is accepted by the mobile redox active domain of the [2Fe-2S] iron-sulfur Rieske protein (FeS protein) and the other goes to cytochrome b. The nature of intermediates in this reaction remains unclear. It is also debatable how the enzyme prevents short-circuiting that could happen if both electrons escape to the FeS protein. Here, I consider a reaction mechanism that (i) agrees with the available experimental data, (ii) entails three traits preventing the short-circuiting in bc1, and (iii) exploits the evident structural similarity of the ubiquinone binding sites in the bc1 and the bacterial photosynthetic reaction center (RC). Based on the latter congruence, it is suggested that the reaction route of ubiquinol oxidation by bc1 is a reversal of that leading to the ubiquinol formation in the RC. The rate-limiting step of ubiquinol oxidation is then the re-location of a ubiquinol molecule from its stand-by site within cytochrome b into a catalytic site, which is formed only transiently, after docking of the mobile redox domain of the FeS protein to cytochrome b. In the catalytic site, the quinone ring is stabilized by Glu-272 of cytochrome b and His-161 of the FeS protein. The short circuiting is prevented as long as: (i) the formed semiquinone anion remains bound to the reduced FeS domain and impedes its undocking, so that the second electron is forced to go to cytochrome b; (ii) even after ubiquinol is fully oxidized, the reduced FeS domain remains docked to cytochrome b until electron(s) pass through cytochrome b; (iii) if cytochrome b becomes (over)reduced, the binding and oxidation of further ubiquinol molecules is hampered; the reason is that the Glu-272 residue is turned towards the reduced hemes of cytochrome b and is protonated to stabilize the surplus negative charge; in this state, this residue cannot participate in the binding/stabilization of a ubiquinol molecule.
Mulkidjanian
Armen Y
AY
Max Planck Institute of Biophysics, Department of Biophysical Chemistry, Max-von-Laue-Str. 3, D-60438 Frankfurt-am-Main, Germany. mulkidjanian@biologie.uni-osnabrueck.de
D020134:Catalytic Domain; D004579:Electron Transport; D014450:Electron Transport Complex III / Q000737:chemistry* / Q000378:metabolism*; D005973:Glutamine; D006639:Histidine; D008954:Models, Biological; D010084:Oxidation-Reduction; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
D005973:Glutamine; D014451:Ubiquinone; D006639:Histidine; D014450:Electron Transport Complex III; C003741:ubiquinol