论文标题
N-甲基D-天冬氨酸受体的甘氨酸结合结构域中的至少三个XENON结合位点
At least three xenon binding sites in the glycine binding domain of the N-methyl D-aspartate receptor
论文作者
论文摘要
氙气可以产生全身麻醉。它的主要蛋白质靶标是N-甲基-D-天冬氨酸受体，这是一种离子型通道在中枢神经系统功能中起关键作用。 允许这种贵重气体具有如此特异性效果的分子机制仍然晦涩难懂，这可能是由于缺乏细节的结构数据而导致的。在此，由于五个独立的分子动力学模拟，在N-甲基-D-天冬氨酸受体的甘氨酸结合结构域中发现了三个不同的结合位点。这些位点中氙气的绝对结合自由能在-8至-14 kJ/mole之间。但是，这显着取决于选择进行计算的蛋白质构象体，这表明如果考虑其他构象异构体，可能会获得更大的值。 这三个站点彼此相邻，其中一个位于甘氨酸地点旁边。这可以解释为什么F758W和F758Y突变可以防止氙气抑制而不会影响甘氨酸结合。
Xenon can produce general anesthesia. Its main protein target is the N-methyl-D-aspartate receptor, a ionotropic channel playing a pivotal role in the function of the central nervous system. The molecular mechanisms allowing this noble gas to have such a specific effect remain obscure, probably as a consequence of the lack of structural data at the atomic level of detail. Herein, as a result of five independent molecular dynamics simulations, three different binding sites were found for xenon in the glycine binding domain of the N-methyl-D-aspartate receptor. The absolute binding free energy of xenon in these sites ranges between -8 and -14 kJ/mole. However, it depends significantly upon the protein conformer chosen for performing the calculation, suggesting that larger values could probably be obtained, if other conformers were considered. These three sites are next to each other, one of them being next to the glycine site. This could explain why the F758W and F758Y mutations can prevent competitive inhibition by xenon without affecting glycine binding.
