Imidazole-imidazole hydrogen bonding in the pH sensing Histidine sidechains of Influenza A M2,Journal of the American Chemical Society

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Imidazole-imidazole hydrogen bonding in the pH sensing Histidine sidechains of Influenza A M2
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2020-01-23 , DOI: 10.1021/jacs.9b10984
Kumar Tekwani Movellan ₁ , Melanie Wegstroth ₁ , Kerstin Overkamp ₁ , Andrei Leonov ₁ , Stefan Becker ₁ , Loren B Andreas ₁

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The arrangement of histidine side chains in influenza A M2 tetramer determines their pKa values, which define pH-controlled proton conduction critical to the virus lifecycle. Both water-associated and hydrogen-bonded imidazole–imidazolium histidine quaternary structures have been proposed, based on crystal structures and NMR chemical shifts, respectively. Here we show, using the conduction domain construct of M2 in lipid bilayers, that the imidazole rings are hydrogen bonded even at a pH of 7.8 in the neutral charge state. An intermolecular 8.9 ± 0.3 Hz 2hJNN hydrogen bond is observed between H37 Nε and Nδ recorded in a fully protonated sample with 100 kHz magic-angle spinning. This interaction could not be detected in the drug-bound sample.

中文翻译：

甲型流感 M2 pH 传感组氨酸侧链中的咪唑-咪唑氢键

甲型流感 M2 四聚体中组氨酸侧链的排列决定了它们的 pKa 值，pKa 值定义了对病毒生命周期至关重要的 pH 控制的质子传导。分别基于晶体结构和核磁共振化学位移，提出了水缔合和氢键合的咪唑-咪唑鎓组氨酸四级结构。在这里，我们使用脂质双层中 M2 的传导域结构证明，即使在中性电荷状态下，咪唑环在 pH 值为 7.8 时也是氢键结合的。在使用 100 kHz 魔角旋转的完全质子化样品中记录的 H37 Nε 和 Nδ 之间观察到分子间 8.9 ± 0.3 Hz 2hJNN 氢键。在药物结合的样品中无法检测到这种相互作用。

更新日期：2020-01-23

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