Mukhopadhyay C, Rao V S
Molecular Biophysics Unit, Indian Institute of Science, Bangalore.
Int J Biol Macromol. 1989 Aug;11(4):194-200. doi: 10.1016/0141-8130(89)90068-8.
The modes of binding of alpha- and beta-anomers of D-galactose, D-fucose and D-glucose to L-arabinose-binding protein (ABP) have been studied by energy minimization using the low resolution (2.4 A) X-ray data of the protein. These studies suggest that these sugars preferentially bind in the alpha-form to ABP, unlike L-arabinose where both alpha- and beta-anomers bind almost equally. The best modes of binding of alpha- and beta-anomers of D-galactose and D-fucose differ slightly in the nature of the possible hydrogen bonds with the protein. The residues Arg 151 and Asn 232 of ABP from bidentate hydrogen bonds with both L-arabinose and D-galactose, but not with D-fucose or D-glucose. However in the case of L-arabinose, Arg 151 forms hydrogen bonds with the hydroxyl group at the C-4 atom and the ring oxygen, whereas in case of D-galactose it forms bonds with the hydroxyl groups at the C-4 and C-6 atoms of the pyranose ring. The calculated conformational energies also predict that D-galactose is a better inhibitor than D-fucose and D-glucose, in agreement with kinetic studies. The weak inhibitor D-glucose binds preferentially to one domain of ABP leading to the formation of a weaker complex. Thus these studies provide information about the most probable binding modes of these sugars and also provide a theoretical explanation for the observed differences in their binding affinities.
利用该蛋白质低分辨率（2.4埃）的X射线数据，通过能量最小化方法研究了D-半乳糖、D-岩藻糖和D-葡萄糖的α-和β-异头物与L-阿拉伯糖结合蛋白（ABP）的结合模式。这些研究表明，与L-阿拉伯糖不同（L-阿拉伯糖的α-和β-异头物结合程度几乎相同），这些糖优先以α-形式与ABP结合。D-半乳糖和D-岩藻糖的α-和β-异头物的最佳结合模式在与蛋白质可能形成的氢键性质上略有不同。ABP的精氨酸151（Arg 151）和天冬酰胺232（Asn 232）与L-阿拉伯糖和D-半乳糖都形成双齿氢键，但不与D-岩藻糖或D-葡萄糖形成氢键。然而，对于L-阿拉伯糖，Arg 151与C-4原子上的羟基和环氧形成氢键，而对于D-半乳糖，它与吡喃糖环的C-4和C-6原子上的羟基形成氢键。计算得到的构象能量还预测，D-半乳糖是比D-岩藻糖和D-葡萄糖更好的抑制剂，这与动力学研究结果一致。弱抑制剂D-葡萄糖优先与ABP的一个结构域结合，导致形成较弱的复合物。因此，这些研究提供了有关这些糖最可能的结合模式的信息，也为观察到的它们结合亲和力的差异提供了理论解释。
