Evolutionary Stability of Salt Bridges Hints Its Contribution to Stability of Proteins
Evolutionary Stability of Salt Bridges Hints Its Contribution to Stability of Proteins
复制标题
盐桥的进化稳定性暗示其对蛋白质稳定性的贡献
DOI：
10.1016/j.csbj.2019.06.022
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发表时间：
2019-01-01
影响因子：
6
通讯作者：
Kaustubh, Bhalerao
中科院分区：
文献类型：
--
作者：
Ban, Xiaofeng;Lahiri, Pratik;Kaustubh, Bhalerao
即使在今天，新设计的盐桥对蛋白质稳定的贡献仍然存在争议。为了解决这一问题，我们从盐桥的空间分布和演化特征两个方面对盐桥进行了研究。首先，我们分析了蛋白质中盐桥的空间分布，阐明了形成盐桥的基本要求。然后，我们从进化的角度出发，研究了盐桥及其邻近残基的进化特征。结果表明，即使在进化压力下，带电残基在序列的某些位置上比其他中性残基出现得更频繁，它们能够形成静电相互作用，从而增加相应氨基酸区域的进化稳定性，从而增强它们对蛋白质稳定性的重要性。作为推论，我们推测新设计的对蛋白质贡献更大的盐桥不仅是合格的盐桥空间分布，而且还需要进一步增加相应氨基酸区域的进化稳定性。根据分析，相应地在来自热葡糖苷地芽孢杆菌STB02的1,4-α-葡聚糖分支酶(EC 2.4.1.18，GBE)中构建了8个突变，其中7个突变提高了GBE的热稳定性。 7个突变的热稳定性增强可能是由于至少一个氨基酸位置是保守的残基位置上额外的盐桥的结果，从而提高了它们对蛋白质稳定性的贡献。 (C) 2019 年作者。由 Elsevier B.V. 代表计算和结构生物技术研究网络出版。
The contribution of newly designed salt bridges to protein stabilization remains controversial even today. In order to solve this problem, we investigated salt bridges from two aspects: spatial distribution and evolutionary characteristics of salt bridges. Firstly, we analyzed spatial distribution of salt bridges in proteins, elucidating the basic requirements of forming salt bridges. Then, from an evolutionary point of view, the evolutionary characteristics of salt bridges as well as their neighboring residues were investigated in our study. The results demonstrate that charged residues appear more frequently than other neutral residues at certain positions of sequence even under evolutionary pressure, which are able to form electrostatic interactions that could increase the evolutionary stability of corresponding amino acid regions, enhancing their importance to stability of proteins. As a corollary, we conjectured that the newly designed salt bridges with more contribution to proteins, not only, are qualified spatial distribution of salt bridges, but also, are needed to further increase the evolutionary stability of corresponding amino acid regions. Based on analysis, the 8 mutations were accordingly constructed in the 1,4-alpha-glucan branching enzyme (EC 2.4.1.18, GBE) from Geobacillus thermoglucosidans STB02, of which 7 mutations improved therrnostability of GBE. The enhanced therrnostability of 7 mutations might be a result of additional salt bridges on residue positions that at least one of amino acids positions is conservative, improving their contribution of stabilization to proteins. (C) 2019 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.