State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023, P. R. China.
J Phys Chem B. 2010 Jun 3;114(21):7383-90. doi: 10.1021/jp9113078.
The unbinding process of three monosaccharides--galactose, glucose, and mannose--from human surfactant protein D (hSP-D) was investigated by the molecular docking and molecular dynamics methods to explore the cause of different dynamic interaction between these monosaccharides and the protein. The results show that the low affinity of galactose for hSP-D is attributed to the different binding conformation from the other two monosaccharides. The sugar coordinates to the calcium ion by the hydroxyl groups in the C2 and C3 atoms, so it cannot form the effective interaction with hSP-D. Glucose and mannose have similar binding conformations with hSP-D. Their difference in the affinity is induced by the interaction between the hydroxyl group in the C2 atom and the residue Asp325. The direction of the hydroxyl group in mannose results in the formation of the hydrogen bond with Asp325 and further makes mannose hydrogen-bond to the residues Glu329 and Arg343 by the hydroxyl groups in the C3, C4, and C6 atoms. As glucose only forms three hydrogen bonds with the residues Glu321, Asn323, and Glu329 by the hydroxyl groups in the C3 and C4 atoms, its interaction with hSP-D is weaker than that of mannose. Thus glucose has a lower energy barrier of dissociation. This work could provide the more penetrating understanding of hSP-D physiological functions.
通过分子对接和分子动力学方法研究了三种单糖（半乳糖、葡萄糖和甘露糖）从人表面活性蛋白 D（hSP-D）上的解结合过程，以探究这些单糖与蛋白质之间不同动态相互作用的原因。结果表明，半乳糖与 hSP-D 的低亲和力归因于其与另外两种单糖不同的结合构象。糖通过 C2 和 C3 原子上的羟基与钙离子配位，因此不能与 hSP-D 形成有效相互作用。葡萄糖和甘露糖与 hSP-D 具有相似的结合构象。它们与亲和力的差异是由 C2 原子上的羟基与残基 Asp325 之间的相互作用引起的。甘露糖中羟基的方向导致其与 Asp325 形成氢键，进一步使甘露糖通过 C3、C4 和 C6 原子上的羟基与残基 Glu329 和 Arg343 形成氢键。由于葡萄糖仅通过 C3 和 C4 原子上的羟基与残基 Glu321、Asn323 和 Glu329 形成三个氢键，其与 hSP-D 的相互作用弱于甘露糖。因此，葡萄糖的解离能垒较低。这项工作可以为 hSP-D 的生理功能提供更深入的理解。
