论文标题
通过蛋白质的S-亚硝基化来控制局部水平控制和功能意义：Kirsten大鼠肉瘤病毒（KRAS）和血红蛋白（HB）
Local Hydration Control and Functional Implications Through S-Nitrosylation of Proteins: Kirsten rat sarcoma virus (KRAS) and Hemoglobin (Hb)
论文作者
论文摘要
S-亚硝基化是半胱氨酸硫醇侧链的共价添加，是一种重要的经换经修饰（PTM），可以影响蛋白质的功能。因此，PTM扩展和多样化蛋白质功能，从而表征PTM在分子水平上的后果引起了极大的关注。尽管可以通过各种直接/间接方法检测到PTM，但它们缺乏研究分子水平修饰的能力。在目前的工作中，局部和全球结构动力学，其相关性，水合结构以及用于WT和S-硝基化的Kirsten大鼠肉瘤病毒（KRAS）和血红蛋白（HB）的红外光谱法的特征是分子动力学模拟的特征。发现对于Kras将NO附加到Cys118中，将其固定在Switch-I区域中具有功能含义的蛋白质，而对于Cys93的HB硝基化，以$β_1$链的链条提高了HB在其T $ _ {0} $ _ {0} $和R $ $ $ $ _} $ _ {4} $ conform conform conform conform consection t $β_1$链中的灵活性。在KRAS中硝基化后，溶剂水的获取降低了40 \％，类似于HB，但是，R $ _4 $的局部水合尚无状态低于T $ _0 $ no。最后，S-亚硝基化导致无伸展的可检测峰，但是，拥挤的IR区域将使对这些频段的实验检测变得困难。
S-nitrosylation, the covalent addition of NO to the thiol side chain of cysteine, is an important post-transitional modification (PTM) that can affect the function of proteins. As such, PTMs extend and diversify protein functions and thus characterizing consequences of PTM at a molecular level is of great interest. Although PTMs can be detected through various direct/indirect methods, they lack the capabilities to investigate the modifications at the molecular level. In the present work local and global structural dynamics, their correlation, the hydration structure, and the infrared spectroscopy for WT and S-nitrosylated Kirsten rat sarcoma virus (KRAS) and Hemoglobin (Hb) are characterized from molecular dynamics simulations. It is found that for KRAS attaching NO to Cys118 rigidifies the protein in the Switch-I region which has functional implications, whereas for Hb nitrosylation at Cys93 at the $β_1$ chain increases the flexibility of secondary structural motives for Hb in its T$_{0}$ and R$_{4}$ conformational substates. Solvent water access decreased by 40\% after nitrosylation in KRAS, similar to Hb for which, however, local hydration of the R$_4$NO state is yet lower than for T$_0$NO. Finally, S-nitrosylation leads to detectable peaks for NO stretch, however, congested IR region will make experimental detection of these bands difficult.
