Selectivity mechanism of magnesium and calcium in cation-binding pocket structures of phosphotyrosine
Selectivity mechanism of magnesium and calcium in cation-binding pocket structures of phosphotyrosine
复制标题
磷酸酪氨酸阳离子结合袋结构中镁和钙的选择性机制
DOI：
10.1103/physreve.101.022410
复制
发表时间：
2020
影响因子：
2.4
通讯作者：
Fang Haiping
中科院分区：
文献类型：
--
作者：
Tu Yusong;Liu Huadong;Shi Guosheng;Zhang Fengmin;Su Tian;Wu Yuanyan;Sun Jiajia;Zhang Lei;Zhang Shengli;Fang Haiping
镁和钙在生物活性中具有重要作用，但对它们的选择性的分子认识仍然缺乏。在这里，基于密度泛函理论计算和从头算分子动力学模拟，我们表明，结合更紧密的磷酸酪氨酸（pTyr）和稳定的pTyr的构象，而结合更灵活的pTyr与结构稳定性较低。选择性的关键是水合阳离子与芳香环之间的阳离子-π相互作用以及阳离子与pTyr侧基之间的协同作用，形成阳离子结合口袋结构，我们称之为辅助基团协同水合阳离子-π相互作用。用紫外吸收光谱和核磁共振谱证实了口袋结构中阳离子-π相互作用的存在和相对强度以及它们的结构稳定性。这一发现为理解生物化学和生理学中各种基本过程的选择性提供了新的视角。
Magnesiumand calciumare of essential importance in biological activity, but the molecular understanding of their selectivity is still lacking. Here, based on density functional theory calculations andab initiomolecular dynamics simulations, we show thatbinds more tightly to phosphotyrosine (pTyr) and stabilizes the conformation of pTyr, whilebinds more flexibly to pTyr with less structural stability. The key for the selectivity is attributed to the cation-π interactions between the hydrated cations and the aromatic ring together with the synergic interaction between the cations and the side groups in pTyr to form a cation-binding pocket structure, which we refer asside-group-synergetic hydrated cation-π interaction. The existence and relative strength of the cation-π interactions in the pocket structures as well as their structural stability have been demonstrated experimentally with ultraviolet (UV) absorption spectra andNMR spectra. The findings offer insight into understanding the selectivity ofandin a variety of biochemical and physiological essential processes.