Mechanism and Catalytic Site Atlas

Step 1. The initial single electron oxidation of the quinol occurs at the Qo site. Glu272 deprotonates the quinol substrate. His161 (bound to a Rieske iron-sulfur cluster) deprotonates the second alcohol group. This initiates a single electron transfer to the Rieske iron-sulfur cluster forming the semi-quinone intermediate.

Step 2. The alkoxide of the semi-quinone intermediate initiates a second single electron transfer (forming the first quinone product) through two heme groups to the quinone substrate, which initiates double bond rearrangement generating a semi-quinone intermediate. The second electron oxidation of the semiquinone occurs at the Qo site. This second electron is transferred to hemes bL (HEM401) and bH (HEM402) in sequence, ending at the quinone in the Qi site. The rotational displacement of Glu295 in the Qo site is favourable for its proton transfer in the next reaction step. The first electron reduction of quinone occurs in the Qi site and is shown here as being concurrent with the second electron oxidation. However, it is unclear of the exact timings of these events. It has been documented [PMID:12885240] that the ubisemiquinone radical produced during this step required an alkaline pH to be stable in the Qi site, consistent with the assumption that both Asp228 and His201 are deprotonated. Furthermore, electron nuclear double resonance experiments showed exchangeable H-bonds bonds to the ubisemiquinone radical, suggesting that the water-mediated H-bonding acts to stabilise the free radical formed.

Step 3. Water deprotonates His161, which initiates a single electron transfer from the Rieske iron-sulfur complex to the heme group of cytochrome-c1. Concurrently, water deprotonates Glu272. This step represents the regeneration of the Qo active site in order that the second quinol molecule may be oxidised. The transfer of the electron from the iron-sulfur cluster is shown here as being a concerted transfer from the iron-sulfur cluster to the cytochrome-c1 and then to the soluble electron acceptor. However, the exact timings of these transfers with respect to the mechanism is unclear. The rotational displacement of Glu272 occurs prior to this step and is favourable for the transfer of its proton to the bulk solvent. The Rieske iron-sulfur cluster (now Fe(II)Fe(III)S2) also undergoes a conformational change to allow it to reach the cytochrome-c1 (HEM3) for the electron transfer. These local movements are clearly complexed with the oxidation of heme bH and ubiquinone reduction.

Step 4. Glu272 deprotonates the second quinol substrate. His161 (bound to a Rieske iron-sulfur cluster) deprotonates the second alcohol group. This initiates a single electron transfer to the Rieske iron-sulfur cluster forming the semi-quinone intermediate. The initial single electron oxidation of the second quinol occurs at the Qo site. This first electron is initially transferred to the Rieske iron-sulfur cluster.

Step 5. The alkoxide of the second semi-quinone intermediate initiates a second single electron transfer (forming the second quinone product) through two heme groups to the semi-quinone substrate, which initiates double bond rearrangement generating the quinol product, that deprotonates Lys228 through a water molecule. The second electron oxidation of the semiquinone occurs at the Qo site. This second electron is transferred to hemes bL (HEM401) and bH (HEM402) in sequence, ending at the semiquinone anion in the Qi site. The rotational displacement of Glu295 in the Qo site is favourable for its proton transfer in the next reaction step. The first electron reduction of quinone occurs in the Qi site and is shown here as being concurrent with the second electron oxidation.

Step 6. Water deprotonates His161, which initiates a single electron transfer from the Rieske iron-sulfur complex to the heme group of cytochrome-c1. Concurrently, water deprotonates Glu272. This step represents the final regeneration of the Qo active site. The transfer of the electron from the iron-sulfur cluster is shown here as being a concerted transfer from the iron-sulfur cluster to the cytochrome-c1 and then to the soluble electron acceptor. However, the exact timings of these transfers with respect to the mechanism is unclear. The rotational displacement of Glu272 occurs prior to this step and is favourable for the transfer of its proton to the bulk solvent. The Rieske iron-sulfur cluster (now Fe(II)Fe(III)S2) also undergoes a conformational change to allow it to reach the cytochrome-c1 (HEM3) for the electron transfer. These local movements are clearly complexed with the oxidation of heme bH and ubiquinone reduction.

Step 7. The catalytic Qi site is regenerated through the uptake of two protons from the negative side of the membrane. These uptake pathways (not explicitly shown) were proposed based on analysis of bound water molecules (Lange et al. [PMID:11726495]).

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