Role of bulk water environment in regulation of functional hydrogen-bond network in photoactive yellow protein
Role of bulk water environment in regulation of functional hydrogen-bond network in photoactive yellow protein
复制标题
本体水环境在光活性黄色蛋白功能性氢键网络调节中的作用
DOI：
10.1021/acs.jpcb.5b07555
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发表时间：
2015
影响因子：
3.3
通讯作者：
Koichi Tamura and Shigehiko Hayashi
中科院分区：
文献类型：
--
作者：
A. Satomura;K. Kuroda;M. Ueda;Koichi Tamura and Shigehiko Hayashi
光敏黄蛋白是一种可溶性感光蛋白，参与趋光性信号转导。发色团，对香豆酸（pCA），和附近的羧基基团的谷氨酸46在活性位点之间的氢键是已知的光活化信号状态的形成中发挥至关重要的作用。由于氢键在活性位点以及广泛的构象变化的蛋白质在形成的信号状态被认为是由水分子控制，我们从理论上研究了大量的水环境的影响功能上重要的氢键通过分子模拟。用量子力学/分子力学（QM/MM）方法对pCA和Glu 46之间质子转移的势能分布进行了理论分析，揭示了体相水的静电屏蔽对氢键电子性质的关键影响.此外，QM/MM自由能几何优化确定了水渗透状态，其中Glu 46与pCA形成假定的低势垒氢键被从本体环境渗透的水分子水合，除了对应于X射线晶体结构的水排斥状态。目前的结果表明，水渗透状态是一个间接的构象亚状态，导致有效形成的信号状态。
Photoactive yellow protein is a soluble photoreceptor protein involved in signal transduction for phototaxis. A hydrogen-bond between the chromophore,p-coumaric acid (pCA), and a nearby carboxyl group of Glu46 at the active site is known to play a crucial role in the formation of the signaling state in the photoactivation. Since the hydrogen-bond at the active site as well as the extensive conformational changes of the protein in the formation of the signaling state are considered to be controlled by water molecules, we theoretically examined influence of bulk water environment on the functionally important hydrogen-bond by means of molecular simulations. Theoretical analysis of potential energy profiles of the proton transfer between pCA and Glu46 with quantum mechanical/molecular mechanical (QM/MM) calculations revealed critical effect of electrostatic screening of bulk water on the electronic character of the hydrogen-bond. Moreover, QM/MM free energy geometry optimizations identified the water-penetrating state where Glu46 forming a putative low-barrier hydrogen-bond with pCA is hydrated by water molecules penetrating from bulk environment in addition to the water-excluded state which corresponds to X-ray crystallographic structures. The present results suggest that the water-penetrating state is a precursory conformational substate that leads to efficient formation of the signaling state.