Conformational Analysis of a High-Mannose-Type Oligosaccharide Displaying Glucosyl Determinant Recognised by Molecular Chaperones Using NMR-Validated Molecular Dynamics Simulation
Conformational Analysis of a High-Mannose-Type Oligosaccharide Displaying Glucosyl Determinant Recognised by Molecular Chaperones Using NMR-Validated Molecular Dynamics Simulation
复制标题
DOI：
10.1002/cbic.201600595
复制
发表时间：
2017-02-16
期刊：
影响因子：
3.2
通讯作者：
Kato, Koichi
中科院分区：
文献类型：
--
作者：
Suzuki, Tatsuya;Kajino, Megumi;Kato, Koichi
探索柔性低聚糖的构象空间对于深入了解其功能机制至关重要。在这里，我们表征了具有末端葡萄糖残基的高甘露糖型十二糖的动态构象，葡萄糖残基是分子伴侣识别的关键决定因素。采用化学酶技术制备十二糖，采用C-13标记和镧系标记，通过核磁共振光谱检测构象依赖性的准磁性效应。核磁共振验证的分子动力学模拟产生了十二糖的动态构象系。这决定了它的空间分布以及末端葡萄糖决定因素的糖苷键构象。此外，将我们的结果与先前报道的晶体学数据进行比较表明，伴侣蛋白与其目标低聚糖的结合涉及诱导配合机制。
Exploration of the conformational spaces of flexible oligosaccharides is essential to gain deeper insights into their functional mechanisms. Here we characterised dynamic conformation of a high-mannose-type dodecasaccharide with a terminal glucose residue, a critical determinant recognised by molecular chaperones. The dodecasaccharide was prepared by our developed chemoenzymatic technique, which uses C-13 labelling and lanthanide tagging to detect conformation-dependent para-magnetic effects by NMR spectroscopy. The NMR-validated molecular dynamics simulation produced the dynamic conformational ensemble of the dodecasaccharide. This determined its spatial distribution as well as the glycosidic linkage conformation of the terminal glucose determinant. Moreover, comparison of our results with previously reported crystallographic data indicates that the chaperone binding to its target oligosaccharides involves an induced-fit mechanism.