Weeks Stephen D, Bouckaert Julie
Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Methods Mol Biol. 2014;1200:511-26. doi: 10.1007/978-1-4939-1292-6_42.
Recent advances in small-angle X-ray scattering (SAXS) have led to the ability to model the glycans on glycoproteins and to obtain the low-resolution solution structures of complexes of lectins bound to multivalent glycan-presenting scaffolds. This progress in SAXS can respond to the increasing interest in the biological action of glycoproteins and lectins and in the design of multivalent glycan-based antagonists. Carbohydrates make up a significant part of the X-ray scattering content in SAXS and should be included in the model together with the protein, whose structure is most often based on a crystal structure or NMR ensemble, to give a far-improved fit with the experimental data. The modeling of the spatial positioning of glycans on proteins or in the architecture of lectin-glycan complexes delivers low-resolution structural information hitherto unmatched by any other method. SAXS data on the bacterial lectin FimH, strongly bound to heptyl α-D-mannose on a sevenfold derivatized β-cyclodextrin, permitted determination of the stoichiometry of the complex and the geometry of the lectin deposition on the multivalent β-cyclodextrin. The SAXS methods can be applied to larger complexes as the technique imposes no limit on the size of the macromolecular assembly in solution.
小角X射线散射（SAXS）的最新进展使得对糖蛋白上的聚糖进行建模以及获得与多价聚糖呈递支架结合的凝集素复合物的低分辨率溶液结构成为可能。SAXS的这一进展能够回应人们对糖蛋白和凝集素的生物学作用以及基于多价聚糖的拮抗剂设计日益增长的兴趣。碳水化合物在SAXS的X射线散射成分中占很大一部分，应与蛋白质一起纳入模型，蛋白质结构通常基于晶体结构或核磁共振集合，以更好地拟合实验数据。对聚糖在蛋白质上或凝集素-聚糖复合物结构中的空间定位进行建模可提供迄今为止其他任何方法都无法比拟的低分辨率结构信息。关于细菌凝集素FimH与七倍衍生化的β-环糊精上的庚基α-D-甘露糖紧密结合的SAXS数据，使得能够确定复合物的化学计量以及凝集素在多价β-环糊精上的沉积几何形状。SAXS方法可应用于更大的复合物，因为该技术对溶液中大分子组装体的大小没有限制。
