Molecular dynamics of the salt dependence of a cold-adapted enzyme: endonuclease I
Molecular dynamics of the salt dependence of a cold-adapted enzyme: endonuclease I
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DOI：
10.1080/07391102.2014.1002007
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发表时间：
2015-02
影响因子：
4.4
通讯作者：
D. Benrezkallah;M. Dauchez;A. Krallafa
中科院分区：
文献类型：
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作者：
D. Benrezkallah;M. Dauchez;A. Krallafa
人们很早就知道盐对球状蛋白稳定性的影响。在目前的研究中，我们将重点研究盐离子对内切酶I酶的结构和活性的影响。在目前的工作中，我们将重点研究离子位置与沙门氏菌弧菌（VsEndA）酶的结构特征之间的关系。我们将集中讨论一些主要问题，如：盐离子如何影响分子结构？酶的活性是什么？哪些特定区域直接参与？为此，我们将使用分子动力学（MD）模拟来研究VsEndA在不同盐浓度下的行为。我们报告了内切酶I酶在五种不同盐浓度下的MD模拟结果。从均方根波动（RMSF）、径向分布函数、接触数和氢键寿命的轨迹分析中可以看出，NaCl浓度的变化会带来明显的差异。结果发现与实验数据很好地一致，我们注意到活性的最佳盐浓度等于425 mM。在此盐浓度下，VsEndA与其他盐浓度相比显示出两个更灵活的环区。在分析这两个特定区域的RMSF时，选择了三个迁移率较高的残基。我们发现研究的结构性质，如径向分布函数、接触数和氢键寿命，与只有两个极性残基的结构柔韧性之间存在相关性。最后，结合目前的工作，通过显溶剂和盐处理，探讨了VsEndA酶盐适应的分子基础。我们的研究结果表明，调节钠/氯离子与蛋白质某些特定环区的相互作用是这种类型的亲冷酶在生理条件下增强催化活性的策略。
The effects of salt on the stability of globular proteins have been known for a long time. In the present investigations, we shall focus on the effect of the salt ions upon the structure and the activity of the endonuclease I enzyme. In the present work, we shall focus on the relationship between ion position and the structural features of the Vibrio salmonicida (VsEndA) enzyme. We will concentrate on major questions such as: how can salt ions affect the molecular structure? What is the activity of the enzyme and which specific regions are directly involved? For that purpose, we will study the behaviour of the VsEndA over different salt concentrations using molecular dynamics (MD) simulations. We report the results of MD simulations of the endonuclease I enzyme at five different salt concentrations. Analysis of trajectories in terms of the root mean square fluctuation (RMSF), radial distribution function, contact numbers and hydrogen bonding lifetimes, indicate distinct differences when changing the concentration of NaCl. Results are found to be in good agreement with experimental data, where we have noted an optimum salt concentration for activity equal to 425 mM. Under this salt concentration, the VsEndA exhibits two more flexible loop regions, compared to the other salt concentrations. When analysing the RMSF of these two specific regions, three residues were selected for their higher mobility. We find a correlation between the structural properties studied here such as the radial distribution function, the contact numbers and the hydrogen bonding lifetimes, and the structural flexibility of only two polar residues. Finally, in the light of the present work, the molecular basis of the salt adaptation of VsEndA enzyme has been explored by mean of explicit solvent and salt treatment. Our results reveal that modulation of the sodium/chloride ions interaction with some specific loop regions of the protein is the strategy followed by this type of psychrophilic enzyme to enhance catalytic activity at the physiological conditions.