Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
Biochem Soc Trans. 2022 Apr 29;50(2):877-893. doi: 10.1042/BST20190963.
Cytochrome (cyt) bc1, bcc and b6f complexes, collectively referred to as cyt bc complexes, are homologous isoprenoid quinol oxidising enzymes present in diverse phylogenetic lineages. Cyt bc1 and bcc complexes are constituents of the electron transport chain (ETC) of cellular respiration, and cyt b6f complex is a component of the photosynthetic ETC. Cyt bc complexes share in general the same Mitchellian Q cycle mechanism, with which they accomplish proton translocation and thus contribute to the generation of proton motive force which drives ATP synthesis. They therefore require a quinol oxidation (Qo) and a quinone reduction (Qi) site. Yet, cyt bc complexes evolved to adapt to specific electrochemical properties of different quinone species and exhibit structural diversity. This review summarises structural information on native quinones and quinone-like inhibitors bound in cyt bc complexes resolved by X-ray crystallography and cryo-EM structures. Although the Qi site architecture of cyt bc1 complex and cyt bcc complex differs considerably, quinone molecules were resolved at the respective Qi sites in very similar distance to haem bH. In contrast, more diverse positions of native quinone molecules were resolved at Qo sites, suggesting multiple quinone binding positions or captured snapshots of trajectories toward the catalytic site. A wide spectrum of inhibitors resolved at Qo or Qi site covers fungicides, antimalarial and antituberculosis medications and drug candidates. The impact of these structures for characterising the Q cycle mechanism, as well as their relevance for the development of medications and agrochemicals are discussed.
细胞色素 (cyt) bc1、bcc 和 b6f 复合物，统称为 cyt bc 复合物，是存在于不同进化谱系中的同源异戊二烯醌氧化酶。cyt bc1 和 bcc 复合物是细胞呼吸电子传递链 (ETC) 的组成部分，而 cyt b6f 复合物是光合 ETC 的组成部分。cyt bc 复合物通常具有相同的米切尔 Q 循环机制，通过该机制它们实现质子转移，从而有助于质子动力势的产生，该动力势驱动 ATP 合成。因此，它们需要一个醌氧化 (Qo) 和一个醌还原 (Qi) 位点。然而，cyt bc 复合物进化以适应不同醌类物质的特定电化学性质，并表现出结构多样性。本综述总结了 X 射线晶体学和 cryo-EM 结构解析的天然醌和类醌抑制剂结合在 cyt bc 复合物中的结构信息。尽管 cyt bc1 复合物和 cyt bcc 复合物的 Qi 位点结构有很大差异，但在非常相似的距离处解析了醌分子与 haem bH 的位置。相比之下，在 Qo 位点解析了更多不同的天然醌分子的位置，这表明存在多个醌结合位置或向催化位点的轨迹捕获快照。在 Qo 或 Qi 位点解析的广泛抑制剂涵盖了杀真菌剂、抗疟药和抗结核药物以及药物候选物。讨论了这些结构对 Q 循环机制的表征的影响，以及它们对药物和农用化学品开发的相关性。
