von Jagow G, Ljungdahl P O, Graf P, Ohnishi T, Trumpower B L
J Biol Chem. 1984 May 25;259(10):6318-26.
Myxothiazol, an antibiotic from Myxococcus fulvus, which inhibits mitochondrial respiration in the bc1 complex of the respiratory chain, has effects on the redox components of isolated succinate-cytochrome c reductase complex which suggest that it interacts with both cytochrome b and the iron-sulfur protein of the bc1 complex. The inhibitor appears to increase the midpoint potentials of cytochromes b-562 and b-566, as indicated by an increase in their reducibility by the succinate/fumarate couple. It also causes a red shift in the optical spectrum of ferrocytochrome b-566, as reported previously (Becker, W. F., Von Jagow , G., Anke , T., Steglisch , W. (1981) FEBS Lett. 132, 329-333). This red shift is enhanced by Triton X-100, and there is no shift in the spectrum of b-562. These results are consistent with evidence that mutations conferring myxothiazol resistance in yeast map to the mitochondrial gene for cytochrome b ( Thierbach , G., and Michaelis, G. (1982) Mol. Gen. Genet. 186, 501-506). In addition, myxothiazol has effects on reduction of the cytochromes b and c1 by succinate or ubiquinol which are identical to those caused by removal of the iron-sulfur protein from the bc1 complex. It blocks reduction of cytochrome c1 during single and multiple turnovers of the bc1 complex, but does not block reduction of the b cytochromes. In the presence of antimycin, it blocks reduction of both cytochromes b and c1. In contrast to antimycin, myxothiazol inhibits oxidant-induced reduction of both b cytochromes and does not inhibit their oxidation by fumarate. Myxothiazol also inhibits reduction of the iron-sulfur protein by ubiquinol and shifts the gx resonance in the EPR spectrum of the iron-sulfur protein from g = 1.79 to 1.76. It does not affect the midpoint potential of the iron-sulfur protein, but does eliminate the increase in midpoint potential which is caused by inhibitory hydroxyquinones which bind to the iron-sulfur protein. The effects of myxothiazol are consistent with a protonmotive Q cycle pathway of electron transfer in which myxothiazol binds to cytochrome b and displaces quinone from the iron-sulfur protein of the bc1 complex. These results suggest either that a myxothiazol-induced conformational change in cytochrome b is transmitted to a quinone binding site on the iron-sulfur protein, or that there is a quinone binding site which consists of peptide domains from both cytochrome b and iron-sulfur protein.
粘噻唑是一种来自黄色粘球菌的抗生素，它能抑制呼吸链bc1复合体中的线粒体呼吸，对分离出的琥珀酸 - 细胞色素c还原酶复合体的氧化还原成分有影响，这表明它与细胞色素b以及bc1复合体的铁硫蛋白相互作用。该抑制剂似乎增加了细胞色素b - 562和b - 566的中点电位，这可通过琥珀酸/延胡索酸对其还原能力的增加来表明。它还会导致亚铁细胞色素b - 566的光谱发生红移，如先前报道（贝克尔，W.F.，冯·雅戈，G.，安克，T.，施特利施，W.（1981年）《欧洲生物化学学会联合会快报》132，329 - 333）。这种红移在Triton X - 100存在时会增强，而b - 562的光谱没有位移。这些结果与以下证据一致：酵母中赋予粘噻唑抗性的突变定位到细胞色素b的线粒体基因（蒂尔巴赫，G.，和米夏埃利斯，G.（1982年）《分子与普通遗传学》186，501 - 506）。此外，粘噻唑对琥珀酸或泛醌醇还原细胞色素b和c1的影响与从bc1复合体中去除铁硫蛋白所引起的影响相同。它在bc1复合体的单次和多次周转过程中阻断细胞色素c1的还原，但不阻断b细胞色素的还原。在抗霉素存在的情况下，它阻断细胞色素b和c1两者的还原。与抗霉素不同，粘噻唑抑制氧化剂诱导的两种b细胞色素的还原，并且不抑制它们被延胡索酸氧化。粘噻唑还抑制泛醌醇对铁硫蛋白的还原，并使铁硫蛋白的电子顺磁共振光谱中的gx共振从g = 1.79移至1.76。它不影响铁硫蛋白的中点电位，但确实消除了与铁硫蛋白结合的抑制性羟基醌所引起的中点电位的增加。粘噻唑的作用与质子动力Q循环电子传递途径一致，在该途径中，粘噻唑与细胞色素b结合并从bc1复合体的铁硫蛋白上取代醌。这些结果表明，要么是粘噻唑诱导的细胞色素b构象变化传递到铁硫蛋白上的醌结合位点，要么是存在一个由细胞色素b和铁硫蛋白的肽结构域组成的醌结合位点。
