Cytochrome c Can Form a Well-Defined Binding Pocket for Hydrocarbons.
Cytochrome c Can Form a Well-Defined Binding Pocket for Hydrocarbons.
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细胞色素 c 可以形成明确的碳氢化合物结合袋。
DOI：
10.1021/jacs.6b10745
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发表时间：
2016-12-28
影响因子：
15
通讯作者：
Bowler BE
中科院分区：
文献类型：
--
作者：
McClelland LJ;Steele HB;Whitby FG;Mou TC;Holley D;Ross JB;Sprang SR;Bowler BE
当细胞色素 c 与线粒体膜中的心磷脂结合时，可以获得过氧化物酶。细胞色素 c 对心磷脂的氧化作用为细胞凋亡的开始提供了早期信号。这种酶-底物复合物的结构是一个颇有争议的问题。我们以 1.7 – 2.0 Å 分辨率展示了酵母 iso-1-细胞色素 c 的结构域交换二聚体的三种结构，其中去垢剂 CYMAL-5、CYMAL-6 和 ω-十一碳烯基-β-D-吡喃麦芽糖苷结合在通道中，该通道将这些去垢剂的烃部分置于血红素旁边。血红素通过与水结合来代替 Met80 来发挥过氧化物酶活性，当细胞色素 c 作为电子载体时，Met80 充当轴向血红素配体。 Tyr67 的羟基距洗涤剂最近的碳原子 3.6 – 4.0 Å，在过氧化物酶活性过程中充当自由基提取的中继。亚油酸（心磷脂最常见的脂肪酸成分）的对接研究表明，亚油酸的 C11 可以与 Tyr67 和血红素相邻，这与脂质组学研究中观察到的氧合模式一致。明确的碳氢化合物结合口袋为细胞色素 c/心磷脂结合的扩展脂质锚定模型提供了原子分辨率证据。酵母与马细胞色素 c 的二聚体解离/缔合动力学表明，哺乳动物细胞色素 c 二聚体在体内的形成需要催化。然而，二聚体结构表明，仅单体细胞色素c的适度变形就足以形成这些去污剂占据的碳氢化合物结合位点。
Cytochrome c can acquire peroxidase when it binds to cardiolipin in mitochondrial membranes. The resulting oxygenation of cardiolipin by cytochrome c provides an early signal for the onset of apoptosis. The structure of this enzyme-substrate complex is a matter of considerable debate. We present three structures at 1.7 – 2.0 Å resolution of a domain-swapped dimer of yeast iso-1-cytochrome c with the detergents, CYMAL-5, CYMAL-6 and ω-undecylenyl-β-D-maltopyranoside bound in a channel that places the hydrocarbon moieties of these detergents next to the heme. The heme is poised for peroxidase activity with water bound in place of Met80, which serves as the axial heme ligand when cytochrome c functions as an electron carrier. The hydroxyl group of Tyr67 sits 3.6 – 4.0 Å from the nearest carbon of the detergents, positioned to act as a relay in radical abstraction during peroxidase activity. Docking studies with linoleic acid, the most common fatty acid component of cardiolipin, show that C11 of linoleic acid can sit adjacent to Tyr67 and the heme, consistent with the oxygenation pattern observed in lipidomics studies. The well-defined hydrocarbon binding pocket provides atomic resolution evidence for the extended lipid anchorage model for cytochrome c/cardiolipin binding. Dimer dissociation/association kinetics for yeast versus equine cytochrome c indicate that formation of mammalian cytochrome c dimers in vivo would require catalysis. However, the dimer structure shows that only a modest deformation of monomeric cytochrome c would suffice to form the hydrocarbon binding site occupied by these detergents.
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影响因子：
8
作者：
Duncan, Michael G.;Williams, Michael D.;Bowler, Bruce E.
通讯作者：
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Borisenko, Grigory
影响因子：
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