The Reversible Opening of Water Channels in Cytochrome c Modulates the Heme Iron Reduction Potential
The Reversible Opening of Water Channels in Cytochrome c Modulates the Heme Iron Reduction Potential
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DOI：
10.1021/ja3030356
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发表时间：
2012-08-22
影响因子：
15
通讯作者：
Daidone, Isabella
中科院分区：
文献类型：
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作者：
Bortolotti, Carlo Augusto;Amadei, Andrea;Daidone, Isabella
蛋白质溶剂的动态相互作用是生命过程的基础，但它们的实验研究仍然非常苛刻。高达数百纳秒的分子动力学模拟可以揭示意外事件，即使是对广泛研究的生物分子也是如此。本文报道了一种计算/实验相结合的方法，揭示了酿酒酵母iso-1-细胞色素c中两个不同的波动腔的可逆开口。这两个通道都允许水进入血红素中心。通过混合量子力学/分子动力学(QM/MD)理论方法，微扰矩阵方法(PMM)，允许达到较长的模拟时间，计算了由于每个空穴的打开而引起的Fe3+/Fe2+对的还原电位的变化，观察到了还原电位随着血红素丙酸酯水合作用的变化而发生的变化。这些变化相对较小，但意义重大，因此可以代表细胞色素c开发的一种工具，用于溶剂驱动的微调其氧化还原功能。
Dynamic protein solvent interactions are fundamental for life processes, but their investigation is still experimentally very demanding. Molecular dynamics simulations up to hundreds of nanoseconds can bring to light unexpected events even for extensively studied biomolecules. This paper reports a combined computational/experimental approach that reveals the reversible opening of two distinct fluctuating cavities in Saccharomyces cerevisiae iso-1-cytochrome c. Both channels allow water access to the heme center. By means of a mixed quantum mechanics/molecular dynamics (QM/MD) theoretical approach, the perturbed matrix method (PMM), that allows to reach long simulation times, changes in the reduction potential of the heme Fe3+/Fe2+ couple induced by the opening of each cavity are calculated Shifts of the reduction potential upon changes in the hydration of the heme propionates are observed These variations are relatively small but significant and could therefore represent a tool developed by cytochrome c for the solvent driven, fine-tuning of its redox functionality.