Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
J Am Chem Soc. 2013 Jul 3;135(26):9877-84. doi: 10.1021/ja4040472. Epub 2013 Jun 19.
Carbohydrate-aromatic interactions mediate many biological processes. However, the structure-energy relationships underpinning direct carbohydrate-aromatic packing interactions in aqueous solution have been difficult to assess experimentally and remain elusive. Here, we determine the structures and folding energetics of chemically synthesized glycoproteins to quantify the contributions of the hydrophobic effect and CH-π interactions to carbohydrate-aromatic packing interactions in proteins. We find that the hydrophobic effect contributes significantly to protein-carbohydrate interactions. Interactions between carbohydrates and aromatic amino acid side chains, however, are supplemented by CH-π interactions. The strengths of experimentally determined carbohydrate CH-π interactions do not correlate with the electrostatic properties of the involved aromatic residues, suggesting that the electrostatic component of CH-π interactions in aqueous solution is small. Thus, tight binding of carbohydrates and aromatic residues is driven by the hydrophobic effect and CH-π interactions featuring a dominating dispersive component.
碳水化合物-芳环相互作用介导了许多生物过程。然而，在水溶液中直接的碳水化合物-芳环包装相互作用的结构-能量关系很难通过实验来评估，目前仍不清楚。在这里，我们确定了化学合成糖蛋白的结构和折叠能，以定量评估疏水作用和 CH-π 相互作用对蛋白质中碳水化合物-芳环包装相互作用的贡献。我们发现疏水作用对蛋白质-碳水化合物相互作用有重要贡献。然而，碳水化合物与芳香族氨基酸侧链之间的相互作用还得到了 CH-π 相互作用的补充。实验确定的碳水化合物 CH-π 相互作用的强度与涉及的芳香族残基的静电特性没有相关性，这表明在水溶液中 CH-π 相互作用的静电分量很小。因此，碳水化合物和芳香族残基的紧密结合是由疏水作用和以分散分量为主导的 CH-π 相互作用驱动的。
