Redox-Driven Conformational Dynamics in a Photosystem-II-Inspired β-Hairpin Maquette Determined through Spectroscopy and Simulation
Redox-Driven Conformational Dynamics in a Photosystem-II-Inspired β-Hairpin Maquette Determined through Spectroscopy and Simulation
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DOI：
10.1021/acs.jpcb.6b09481
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发表时间：
2017-04-20
影响因子：
3.3
通讯作者：
Gumbart, James C.
中科院分区：
文献类型：
--
作者：
Hwang, Hyea;McCaslin, Tyler G.;Gumbart, James C.
基于酪氨酸的自由基转移在光合作用、呼吸作用和DNA合成中起重要作用。自由基转移可以通过电子转移（ET）或质子耦合电子转移（PCET）发生，具体取决于pH值。周围蛋白质基质的可逆构象变化可能会控制自由基中间体的反应性。从头设计的肽A是合成的18个氨基酸的β-发夹，其含有单个酪氨酸（Y 5）并在Y 5和交叉链组氨酸（H14）之间进行动力学显著的PCET反应。在肽A中，在UV共振拉曼（UVRR）光谱中观察到酰胺II'（CN）变化，与酪氨酸ET和PCET相关;这些条带先前归因于二级结构的可逆变化。在这里，我们使用分子动力学模拟来定义肽A及其H14到环己基丙氨酸变体肽C中的这种构象变化。三种不同的Y 5电荷状态，酪氨酸（YH），酪氨酸（Y-），和中性酪氨酰基自由基（Y中心点），被认为是。模拟结果表明，肽A-YH和A-Y-保留了二级结构和非共价相互作用，而A-Y中心点是不稳定的。相比之下，由于Y 5-H14 π-π相互作用的丧失，肽C-Y-和肽C-Y中心点都是不稳定的。这些模拟结果与之前的UVRR实验结果是一致的两个β-发夹。此外，他们证明了使用固定电荷力场模拟的能力，以准确地捕获β链肽中氧化还原相关的构象动力学。
Tyrosine-based radical transfer plays an important role in photosynthesis, respiration, and DNA synthesis. Radical transfer can occur either by electron transfer (ET) or proton coupled electron transfer (PCET), depending on the pH. Reversible conformational changes in the surrounding protein matrix may control reactivity of radical intermediates. De novo designed Peptide A is a synthetic 18 amino-acid beta-hairpin, which contains a single tyrosine (Y5) and carries out a kinetically significant PCET reaction between Y5 and a cross-strand histidine (H14). In Peptide A, amide II' (CN) changes are observed in the UV resonance Raman (UVRR) spectrum, associated with tyrosine ET and PCET; these bands were attributed previously to a reversible change in secondary structure. Here, we use molecular dynamics simulations to define this conformational change in Peptide A and its H14-to-cyclohexylalanine variant, Peptide C. Three different Y5 charge states, tyrosine (YH), tyrosinate (Y-), and neutral tyrosyl radical (Y center dot), are considered. The simulations show that Peptide A-YH and A-Y- retain secondary structure and noncovalent interactions, whereas A-Y center dot is unstable. In contrast, both Peptide C-Y- and Peptide C-Y center dot are unstable, due to the loss of the Y5-H14 pi-pi interaction. These simulations are consistent with previous UVRR experimental results on the two beta-hairpins. Furthermore, they demonstrate the ability of simulations using fixed-charge force fields to accurately capture redox-linked conformational dynamics in a beta-strand peptide.