在influenza A M2的pH感应胺侧链中,imidazole与imidazole的结
Kumar Tekwani Movellan1, Melanie Wegstroth1, Kerstin Overkamp1
1Department of NMR Based Structural Biology , Max Planck Institute for Biophysical Chemistry , Am Fassberg 11 , Göttingen 37077 , Germany.
Journal of the American Chemical Society
|January 24, 2020
概括
流感A M2通道的希斯提丁侧链在中性状态下形成键,影响病毒复制所必需的依赖pH的质子导电. 这一发现影响了对M2通道功能和药物相互作用的理解.
科学领域:
- 结构生物学
- 病毒学
- 生物物理
背景情况:
- 流感A M2蛋白质形成了对病毒脱涂至关重要的质子通道.
- 希斯蒂丁侧链质子化状态 (pKa值) 调节M2通道活动.
- 之前的模型提出了与水相结合或与相结合的胺结构.
研究的目的:
- 调查M2通道导电域中的胺侧链的结构排列.
- 在生理pH下确定胺残留物的质子化状态和相互作用.
- 阐明M2通道中依赖pH的质子导电机制.
主要方法:
- 使用M2蛋白质的导电域构造,将其复制成脂质双层.
- 采用固态核磁共振 (NMR) 光谱仪,使用100kHz的魔角旋转.
- 测量了分子间2hJNN合常数以探测结相互作用.
主要成果:
- 观察到,即使在中性电荷状态下pH值为7.8时,histidine残留物中的imidazole环也会与结合.
- 在H37Nε和Nδ之间检测到一个分子间的8.9±0.3Hz2hJNN键.
- 在与药物结合的M2通道样本中没有这种特定的键相互作用.
结论:
- 在M2通道中的histidine残留物在中性pH下保持与结合的四级结构.
- 这种内在的键影响pKa值和pH依赖的质子导电.
- 观察到的相互作用为M2通道关口和潜在的药物结合部位提供了新的见解.
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