Department of Chemistry, University of Calcutta, 92, A.P.C. Road, Kolkata 700 009, India.
Carbohydr Res. 2012 Feb 15;349:59-72. doi: 10.1016/j.carres.2011.11.021. Epub 2011 Dec 3.
The binding of serum mannose-binding protein A (MBP-A) to high mannose N-linked glycoproteins, present on the surface of microorganism, activates the complement system. It is very important to explore the overall conformations of these ligands in the binding site of the MBP-A, which is very much dependent on the conformation of the manno-di-, tri- and the penta-saccharides that represent the component structures of these high-mannose type oligosaccharides. Herein, we report the possible conformations of α-(1→6)-linked dimannoside, benzyl-substituted trimannoside and core pentamannoside of the N-linked glycan in the binding site of MBP-A, with the help of molecular dynamics simulations. The results indicate that for all three ligands in addition to the non-reducing terminal mannose moiety the reducing moieties also interact with protein. Binding free energy calculations also indicate that the benzyl-substituted trisaccharide has higher affinity in comparison to the methyl substituted one. We have also found some conformers of the pentasaccharide, which have higher binding affinity than the monosaccharide.
血清甘露糖结合蛋白 A（MBP-A）与微生物表面存在的高甘露糖 N-连接糖蛋白的结合会激活补体系统。探索 MBP-A 结合位点中这些配体的整体构象非常重要，这非常依赖于代表这些高甘露糖型寡糖组成结构的甘露二糖、三糖和五糖的构象。在此，我们借助分子动力学模拟，报道了 N-连接糖基中 α-(1→6)-连接二甘露糖苷、苄基取代的三甘露糖苷和核心五甘露糖苷在 MBP-A 结合位点中的可能构象。结果表明，对于所有三种配体，除了非还原末端甘露糖部分外，还原部分也与蛋白质相互作用。结合自由能计算也表明，与甲基取代的三糖相比，苄基取代的三糖具有更高的亲和力。我们还发现了一些五糖的构象，它们比单糖具有更高的结合亲和力。
