Features of S-nitrosylation based on statistical analysis and molecular dynamics simulation: cysteine acidity, surrounding basicity, steric hindrance and local flexibility
Features of S-nitrosylation based on statistical analysis and molecular dynamics simulation: cysteine acidity, surrounding basicity, steric hindrance and local flexibility
复制标题
基于统计分析和分子动力学模拟的S-亚硝基化特征：半胱氨酸酸性、周围碱性、空间位阻和局部柔性
DOI：
10.1039/c4mb00322e
复制
发表时间：
2014-01-01
影响因子：
--
通讯作者：
Zhao, Yi-Lei
中科院分区：
文献类型：
--
作者：
Cheng, Shangli;Shi, Ting;Zhao, Yi-Lei
S-亚硝基化参与蛋白质功能调节和细胞信号转导。尽管人们付出了巨大的努力，但S-亚硝基化的分子机制尚未完全清楚。在这项工作中，我们对213个具有S-亚硝基化半胱氨酸位点的蛋白质结构进行了调查，并以血红蛋白的分子动力学模拟作为案例研究。结果发现，S-亚硝基化半胱氨酸表现出较低的pK(a)、较高的碱性残基数量、较低的邻域大体积残基数量以及相对较高的灵活性。血红蛋白的案例研究表明，与T态血红蛋白相比，R态血红蛋白中的Cys beta 93具有上述结构特征，这与之前报道的R态更容易发生S-亚硝基化反应一致。此外，碱性残基靠近dep-R-状态血红蛋白中的Cys β 93，而大体积残基靠近dep-T-状态中的Cys β 93。利用半胱氨酸酸性、周围碱性、空间位阻和局部柔性这四个特征，构建了S-亚硝基化的3维模型，解释了61.9%的S-亚硝基化半胱氨酸和58.1%的非S-亚硝基化半胱氨酸。我们的研究表明，半胱氨酸去质子化是蛋白质 S-亚硝基化的先决条件，这些特征可能有助于识别蛋白质 S-亚硝基化的特异性。
S-Nitrosylation is involved in protein functional regulation and cellular signal transduction. Although intensive efforts have been made, the molecular mechanisms of S-nitrosylation have not yet been fully understood. In this work, we carried out a survey on 213 protein structures with S-nitrosylated cysteine sites and molecular dynamic simulations of hemoglobin as a case study. It was observed that the S-nitrosylated cysteines showed a lower pK(a), a higher population of basic residues, a lower population of big-volume residues in the neighborhood, and relatively higher flexibility. The case study of hemoglobin showed that, compared to that in the T-state, Cys beta 93 in the R-state hemoglobin possessed the above structural features, in agreement with the previous report that the R-state was more reactive in S-nitrosylation. Moreover, basic residues moved closer to the Cys beta 93 in the dep-R-state hemoglobin, while big-volume residues approached the Cys beta 93 in the dep-T-state. Using the four characteristics, i.e. cysteine acidity, surrounding basicity, steric hindrance, and local flexibility, a 3-dimensional model of S-nitrosylation was constructed to explain 61.9% of the S-nitrosylated and 58.1% of the non-S-nitrosylated cysteines. Our study suggests that cysteine deprotonation is a prerequisite for protein S-nitrosylation, and these characteristics might be useful in identifying specificity of protein S-nitrosylation.