Matsuura K, Bowyer J R, Ohnishi T, Dutton P L
J Biol Chem. 1983 Feb 10;258(3):1571-9.
3-Alkyl-2-hydroxy-1,4-naphthoquinones (alkyl-HNQ) inhibit Rieske iron-sulfur cluster (Rieske FeS) oxidation and cytochrome b reduction in ubiquinol-cytochrome c oxidoreductase. The effects are the same as those of 5-undecyl-6-hydroxy-4,7-dioxobenzothiazole. Concentrations for 50% inhibition in chromatophores of Rhodopseudomonas sphaeroides (at 0.4 microM reaction center) are 2 microM for undecyl-, 3 microM for octyl-, and 40 microM for pentyl-substituted hydroxynaphthoquinones. The ethyl-substituted and unsubstituted derivatives do not inhibit electron transfer below 2 mM. In chromatophores in which the ubiquinone is partially extracted by isooctane (leaving 4 ubiquinones/reaction center), undecyl-HNQ is effective at 2.5 times lower concentration than in normal chromatophores (30 ubiquinones/reaction center). This observation suggests that the binding of the inhibitor is competitive with ubiquinone. Undecyl-HNQ eliminates the effect that the ubiquinone redox state has on the line shape of the EPR signal of Rieske FeS. This supports the idea that alkyl-HNQ shares a common binding site with ubiquinone which is closely associated with Rieske FeS. The ubiquinone in question has a midpoint oxidation-reduction potential at pH 7 of 90 mV with a -60 mV/pH unit dependency. This value matches that of the ubiquinone pool rather than that of ubiquinone Z, which is functionally recognized as a component "between" cytochrome b and Rieske FeS. When Rieske FeS is oxidized, a 20 times higher concentration of undecyl-HNQ is required for the electron transfer inhibition. This is consistent with the observation that the binding of the inhibitor shifts the midpoint oxidation-reduction potential of Rieske FeS about 60 mV higher, which in turn means that the inhibitor binds about 10 times stronger to the site when Rieske FeS is reduced than when it is oxidized. The observations suggest that 3-alkyl-2-hydroxy-1,4-naphthoquinones inhibit electron transfer by acting as ubiquinone antagonists at a site closely associated with Rieske FeS.
3-烷基-2-羟基-1,4-萘醌（烷基-HNQ）可抑制泛醇-细胞色素c氧化还原酶中 Rieske 铁硫簇（Rieske FeS）的氧化以及细胞色素b的还原。其作用效果与5-十一烷基-6-羟基-4,7-二氧代苯并噻唑相同。在球形红假单胞菌的载色体中（反应中心浓度为0.4微摩尔），50%抑制率时，十一烷基取代的羟基萘醌浓度为2微摩尔，辛基取代的为3微摩尔，戊基取代的为40微摩尔。乙基取代和未取代的衍生物在浓度低于2毫摩尔时不抑制电子传递。在泛醌被异辛烷部分提取（每个反应中心留下4个泛醌）的载色体中，十一烷基-HNQ发挥作用的浓度比正常载色体（每个反应中心30个泛醌）低2.5倍。这一观察结果表明抑制剂的结合与泛醌具有竞争性。十一烷基-HNQ消除了泛醌氧化还原状态对 Rieske FeS 的电子顺磁共振信号线形的影响。这支持了烷基-HNQ与泛醌共享一个与 Rieske FeS 紧密相关的共同结合位点的观点。所讨论的泛醌在pH 7时的中点氧化还原电位为90毫伏，具有-60毫伏/单位pH的依赖性。该值与泛醌池的值匹配，而不是与泛醌Z的值匹配，泛醌Z在功能上被认为是细胞色素b和 Rieske FeS之间的一个成分。当 Rieske FeS 被氧化时，抑制电子传递所需的十一烷基-HNQ浓度要高20倍。这与抑制剂的结合使 Rieske FeS 的中点氧化还原电位升高约60毫伏的观察结果一致，这反过来意味着抑制剂在 Rieske FeS 被还原时与该位点的结合比其被氧化时强约10倍。这些观察结果表明，3-烷基-2-羟基-1,4-萘醌通过在与 Rieske FeS 紧密相关的位点上作为泛醌拮抗剂来抑制电子传递。
