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首页> 外文期刊>Biochemistry >Architecture of the Q_o Site of the Cytochrome bc_1 Complex Proded by Superoxide Production
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Architecture of the Q_o Site of the Cytochrome bc_1 Complex Proded by Superoxide Production

机译：超氧化物生产推动的细胞色素bc_1复合物Q_o位点的结构

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Although several X-ary structures have been determined for the mitochondrial cytochrome (cyt) bc_1 complex none yet shows the position of hte substrate ubiquinol in hte quinol oxidase (Q_o) site.In this study the interaction of molecular oxygen with the reactive intermediate Q_o semiquinone is used to probe the Q_o site It has been known for some time that partial turnover of the cyt bc_1 complex in the presence of antimycin A a Q_i site inhibitor results in accumulation of a semiquinone at the Q_o site which can reduce O_2 to superoxide(O_2~.-).It was more erecently shown that myxothiazolwhich binds colse ot the cyt b_L heme in hte procimal Q_o nicfhe also induces O_2~.- production In this work it is shown that in addition t myxothizol a number of other proximal Q_o inhibitors [including(E)-beta-methoxyacylatestlbene,mucidin and famoxadone] also induce O_2~.- production in hte isolated yeast cyt bc_1 complex at ~50% of the V_max observed in hte presence of antimycin A It is proposed that proximal Q_o site inhibitors induce O_2~.- production because they allow formation but not oxidation of the semiquinone at the distal niche of the Q_o site pocket The apparent K_m for ubiquinol at the Q_o site in the presence of proximal Q_o site inhibitors suggets that the distal niche of the Q_o prcket can cat as a fully independent quion binding and oxidation site Together with the X-ray structures dthese results suggest substrate ubiqinol binds in a fashion similar ot hte of sigmatellin with H-bonds betwen H161 of hte Rieske iron-sulfur protin and E272 of the cyt b jprotein When modeled in htis way mucidin and ubiquinol can bind simultanusly ot the Q_o site with virtually no steric hindrance whereas progreeively bulkier inhibitors exhibit increasing overlpa the fact that partial turnover of the Q_o site is possible cven with bound procimal Q_o site inhibitors is consitstent wiht the jparticipation of two separate functional Q_o binding niches occupied simultneously or sequentially.
机译：尽管已经确定了线粒体细胞色素（cyt）bc_1配合物的几种X-ary结构，但仍未显示泛醇在羟喹啉氧化酶（Q_o）位点的位置。在这项研究中，分子氧与反应性中间体Q_o半醌的相互作用用于探测Q_o位点一段时间以来，人们已经知道在抗霉素A存在下，cyt bc_1复合物的部分周转会导致Q_i位点抑制剂在Q_o位点处积聚半醌，从而将O_2还原为超氧化物（O_2 〜.-）。最近发现，在最初的Q_o nicfhe中，与胞质b_L血红素结合的甲噻唑也可诱导O_2〜.-的产生。在这项工作中，还显示了除[mythothizol]外还有许多其他近端Q_o抑制剂[包括（E）-β-甲氧基酰化苯乙烯，粘环蛋白和法莫沙酮]也会在分离的酵母cyt bc_1复合物中诱导O_2〜.-在抗霉素A存在下观察到的V_max的〜50％时产生。帽子近端Q_o部位抑制剂可诱导O_2〜.-产生，因为它们允许在Q_o部位口袋的远端壁formation形成但不氧化半醌。存在近端Q_o部位抑制剂的情况下，Q_o部位泛醌的表观K_m提示： Q_o囊的远端壁iche可能是完全独立的基团结合和氧化位点，再加上X射线结构，这些结果表明底物泛醇与sigmatellin的结合方式类似于Rieske铁-硫的H161之间的氢键。 cyt b J蛋白的蛋白和E272当以高方式建模时，粘蛋白和泛醇可以同时与Q_o位点结合，而几乎没有空间位阻，而体积更大的抑制剂则表现出越来越高的重叠，这是由于Q_o位点的部分转换可能与有限的过程结合而实现。 Q_o部位抑制剂是同时或继发的两个单独的功能性Q_o结合位点的参与所必需的莉莉

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