CONFORMATIONAL AND PROTEIN BINDING ANALYSIS OF OLIGOSACCHARIDES

低聚糖的构象和蛋白质结合分析

• 批准号: 3752042
• 负责人: P K QASBA
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3752042
• 关键词: N acetylglucosamine; carbohydrate receptor; carbohydrate structure; chemical binding; computer simulation; galactose; glycosyltransferase; lectin; ligands; molecular dynamics; molecular energy level; molecular site; monosaccharides; oligosaccharides; receptor binding; solutions

Diverse oligosaccharide structures that are generated with the help of specific glycosyltransferases from a relatively small number of saccharide units, have an enormous potential for encoding information. This information content for a given oligosaccharide is increased furthermore by the existence of several conformers which exist in equilibrium in solution that have been implicated in several biological functions. Most of the experimental studies in solution give a time averaged conformation, closely resembling the global energy minimum conformer, that however, need not be the bioactive conformer. To have a precise idea about the bioactive conformer, it is essential to have the information about all the conformers which are accessible by this particular oligosaccharide. We have applied molecular dynamics technique to study all the possible conformations of some bi- and triantennary oligosaccharides that are the ligands of glycosyltransferases and of asialoglycoprotein cell surface receptor (ASGP-R). Most of the earlier studies on the conformational behavior of oligosaccharides were limited to the study of individual di- and trisaccharide fragments which constitute the actual oligosaccharides present on glycoproteins. Molecular dynamics simulation of the molecules for one nano second by considering all the monosaccharides simultaneously has provided a wealth of information about the conformational preferences of these molecules. The results show that contrary to earlier beliefs oligosaccharides show considerable amount of flexibility. The relative distance and orientation of the galactose residues on the 1,2- and 1,4- branches of the 1,3-arm of triantennary oligosaccharide are invariant during most of the simulation period. Contrary to the 1,3 arm, the 1,6 arm is close to the GlcNAc residues of the core oligosaccharide structure. Binding of the 1,3-arm may bring about a conformational change in the 1,6- arm and lead to its interaction with a lectin, e.g ASGP-R, providing additional binding energy.

在以下物质的帮助下产生的各种寡糖结构 来自相对少量糖的特异性糖基转移酶 单位，具有编码信息的巨大潜力。 这 给定寡糖的信息含量进一步增加 由于存在几种处于平衡状态的构象异构体， 这些解决方案涉及几种生物功能。 最 在溶液中的实验研究给出了时间平均构象， 与全局能量最小构象非常相似，然而，需要 而不是生物活性构象异构体。 要想准确地了解 生物活性构象，它是必不可少的，有关于所有的信息， 这种特殊的寡糖可以接触到的构象异构体。 我们 应用分子动力学技术研究了所有可能的 一些双触角和三触角寡糖的构象， 糖基转移酶和脱唾液酸糖蛋白细胞表面的配体 受体（ASGP-R）。 大多数关于构象的早期研究 低聚糖的行为仅限于研究单个的二- 和构成实际寡糖的三糖片段 存在于糖蛋白中。 分子动力学模拟 同时考虑所有的单糖， 已经提供了大量关于构象偏好的信息 of these molecules分子. 结果表明，与早期的信念相反， 寡糖显示出相当大的柔性。 的相对 1，2-和1，4-半乳糖残基的距离和方向 三触角寡糖的1，3-臂的分支是不变的 在大部分的模拟时间里。 与1，3臂相反，1，6臂 臂靠近核心寡糖结构的GlcNAc残基。 1，3-臂的结合可能会导致1，6-臂的构象变化。 臂并导致其与凝集素，例如ASGP-R相互作用， 额外的结合能。