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Atomistic determinants of co-enzyme Q reduction at the Q i -site of the cytochrome bc 1 complex

View Article: PubMed Central - PubMed

ABSTRACT

The cytochrome (cyt) bc1 complex is an integral component of the respiratory electron transfer chain sustaining the energy needs of organisms ranging from humans to bacteria. Due to its ubiquitous role in the energy metabolism, both the oxidation and reduction of the enzyme’s substrate co-enzyme Q has been studied vigorously. Here, this vast amount of data is reassessed after probing the substrate reduction steps at the Qi-site of the cyt bc1 complex of Rhodobacter capsulatus using atomistic molecular dynamics simulations. The simulations suggest that the Lys251 side chain could rotate into the Qi-site to facilitate binding of half-protonated semiquinone – a reaction intermediate that is potentially formed during substrate reduction. At this bent pose, the Lys251 forms a salt bridge with the Asp252, thus making direct proton transfer possible. In the neutral state, the lysine side chain stays close to the conserved binding location of cardiolipin (CL). This back-and-forth motion between the CL and Asp252 indicates that Lys251 functions as a proton shuttle controlled by pH-dependent negative feedback. The CL/K/D switching, which represents a refinement to the previously described CL/K pathway, fine-tunes the proton transfer process. Lastly, the simulation data was used to formulate a mechanism for reducing the substrate at the Qi-site.

No MeSH data available.


The proposed sequential quinone reduction mechanism at the Qi-site of the cyt bc1 complex.Those protons (H+) that are subject to transport (*) are shown in orange. For cardiolipin (CL) residing at the periphery is shown only the phosphate group. Note that the proton transfers between the peripheral CL and Lys251 do not necessarily involve water molecules. H-bonds are shown as magenta dotted lines. It is noteworthy that, if the two electrons are acquired separate from the H+ transfers (according to the concomittand proton transfer theory)17, it is unlikely that Lys251 rotation would play a role in the substrate binding (Fig. 5).
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f5: The proposed sequential quinone reduction mechanism at the Qi-site of the cyt bc1 complex.Those protons (H+) that are subject to transport (*) are shown in orange. For cardiolipin (CL) residing at the periphery is shown only the phosphate group. Note that the proton transfers between the peripheral CL and Lys251 do not necessarily involve water molecules. H-bonds are shown as magenta dotted lines. It is noteworthy that, if the two electrons are acquired separate from the H+ transfers (according to the concomittand proton transfer theory)17, it is unlikely that Lys251 rotation would play a role in the substrate binding (Fig. 5).

Mentions: Based on the simulations (Fig. 2), prior mutagenesis experiments18 and X-ray crystallographic data (Tables S1,S5, and S7), the sequential Q reduction is suggested to happen accordingly (Fig. 5):


Atomistic determinants of co-enzyme Q reduction at the Q i -site of the cytochrome bc 1 complex
The proposed sequential quinone reduction mechanism at the Qi-site of the cyt bc1 complex.Those protons (H+) that are subject to transport (*) are shown in orange. For cardiolipin (CL) residing at the periphery is shown only the phosphate group. Note that the proton transfers between the peripheral CL and Lys251 do not necessarily involve water molecules. H-bonds are shown as magenta dotted lines. It is noteworthy that, if the two electrons are acquired separate from the H+ transfers (according to the concomittand proton transfer theory)17, it is unlikely that Lys251 rotation would play a role in the substrate binding (Fig. 5).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5035994&req=5

f5: The proposed sequential quinone reduction mechanism at the Qi-site of the cyt bc1 complex.Those protons (H+) that are subject to transport (*) are shown in orange. For cardiolipin (CL) residing at the periphery is shown only the phosphate group. Note that the proton transfers between the peripheral CL and Lys251 do not necessarily involve water molecules. H-bonds are shown as magenta dotted lines. It is noteworthy that, if the two electrons are acquired separate from the H+ transfers (according to the concomittand proton transfer theory)17, it is unlikely that Lys251 rotation would play a role in the substrate binding (Fig. 5).
Mentions: Based on the simulations (Fig. 2), prior mutagenesis experiments18 and X-ray crystallographic data (Tables S1,S5, and S7), the sequential Q reduction is suggested to happen accordingly (Fig. 5):

View Article: PubMed Central - PubMed

ABSTRACT

The cytochrome (cyt) bc1 complex is an integral component of the respiratory electron transfer chain sustaining the energy needs of organisms ranging from humans to bacteria. Due to its ubiquitous role in the energy metabolism, both the oxidation and reduction of the enzyme’s substrate co-enzyme Q has been studied vigorously. Here, this vast amount of data is reassessed after probing the substrate reduction steps at the Qi-site of the cyt bc1 complex of Rhodobacter capsulatus using atomistic molecular dynamics simulations. The simulations suggest that the Lys251 side chain could rotate into the Qi-site to facilitate binding of half-protonated semiquinone – a reaction intermediate that is potentially formed during substrate reduction. At this bent pose, the Lys251 forms a salt bridge with the Asp252, thus making direct proton transfer possible. In the neutral state, the lysine side chain stays close to the conserved binding location of cardiolipin (CL). This back-and-forth motion between the CL and Asp252 indicates that Lys251 functions as a proton shuttle controlled by pH-dependent negative feedback. The CL/K/D switching, which represents a refinement to the previously described CL/K pathway, fine-tunes the proton transfer process. Lastly, the simulation data was used to formulate a mechanism for reducing the substrate at the Qi-site.

No MeSH data available.