The Dependence of Carbohydrate-Aromatic Interaction Strengths on the Structure of the Carbohydrate.
The Dependence of Carbohydrate-Aromatic Interaction Strengths on the Structure of the Carbohydrate.
复制标题
碳水化合物 - 芳族相互作用强度对碳水化合物结构的依赖性。
DOI：
10.1021/jacs.6b02879
复制
发表时间：
2016-06-22
影响因子：
15
通讯作者：
Kelly JW
中科院分区：
文献类型：
--
作者：
Hsu CH;Park S;Mortenson DE;Foley BL;Wang X;Woods RJ;Case DA;Powers ET;Wong CH;Dyson HJ;Kelly JW
蛋白质和碳水化合物之间的相互作用在生物学中无处不在。因此，了解决定它们的亲和力和选择性的因素是相应重要的。在此，我们确定了n -糖蛋白宿主中一系列单糖和靠近糖基化位点的芳香环之间分子内相互作用的相对强度。我们利用增强的芳香序列（在一些n -糖蛋白的反转中发现的结构基序）来促进面对面的单糖-芳香相互作用。使用蛋白质宿主是因为折叠能量对单糖身份的依赖可以准确测量，以评估碳水化合物-芳香相互作用的强度。我们的数据表明，碳水化合物-芳香相互作用的强度受到糖的立体化学和吡喃糖环上取代基性质的变化的适度影响。半乳糖与葡萄糖、n -乙酰氨基葡萄糖（GlcNAc）和甘露糖之间的相互作用似乎是最弱的，而与糖-芳香相互作用则是最强的。对几种含单糖n -糖蛋白的核磁共振溶液结构进行了求解，进一步了解了单糖-芳香相互作用能异同的来源。在我们的n -糖蛋白宿主环境中，单糖的过乙酰化大大增加了糖-芳香相互作用的强度。最后，我们根据最近关于静电对CH -π相互作用的贡献的文献讨论了我们的结果，并推测我们的观察结果暗示了GlcNAc作为真核生物中n -链聚糖附着在糖蛋白上的单糖的绝对守恒。
Interactions between proteins and carbohydrates are ubiquitous in biology. Therefore, understanding the factors that determine their affinity and selectivity are correspondingly important. Herein, we have determined the relative strengths of intramolecular interactions between a series of monosaccharides and an aromatic ring close to the glycosylation site in an N-glycoprotein host. We employed the enhanced aromatic sequon, a structural motif found in the reverse turns of some N-glycoproteins, to facilitate face-to-face monosaccharide–aromatic interactions. A protein host was used because the dependence of the folding energetics on the identity of the monosaccharide can be accurately measured to assess the strength of the carbohydrate–aromatic interaction. Our data demonstrate that the carbohydrate–aromatic interaction strengths are moderately affected by changes in the stereochemistry and identity of the substituents on the pyranose rings of the sugars. Galactose seems to make the weakest and allose the strongest sugar–aromatic interactions, with glucose, N-acetylglucosamine (GlcNAc) and mannose in between. The NMR solution structures of several of the monosaccharide-containing N-glycoproteins were solved to further understand the origins of the similarities and differences between the monosaccharide–aromatic interaction energies. Peracetylation of the monosaccharides substantially increases the strength of the sugar–aromatic interaction in the context of our N-glycoprotein host. Finally, we discuss our results in light of recent literature regarding the contribution of electrostatics to CH–π interactions and speculate on what our observations imply about the absolute conservation of GlcNAc as the monosaccharide through which N-linked glycans are attached to glycoproteins in eukaryotes.