Involvement of water in carbohydrate-protein binding
Involvement of water in carbohydrate-protein binding
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DOI：
10.1021/ja004315q
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发表时间：
2001-12-12
影响因子：
15
通讯作者：
Boons, GJ
中科院分区：
文献类型：
--
作者：
Clarke, C;Woods, RJ;Boons, GJ
研究了三甘露糖苷1和2与Con A的相互作用，以揭示有序水分子的置换对蛋白质-配体络合热力学参数的影响。三糖2是1的衍生物。其中中心甘露糖单元C-2位的羟基被羟乙基部分取代。结合后，该部分取代ConA结合位点中存在的保守水分子。通过核磁共振波谱和分子动力学模拟的结构研究表明，这两种化合物具有非常相似的溶液构象性质。对Con A与1和2的复合物的MD模拟表明，2的羟乙基侧链可以与蛋白质结合位点建立与1与Con A复合物中水分子介导的相同的低能构象氢键。等温滴定微量热法（ITC）的测量结果表明，2具有更有利的结合熵相比，1。这一术语是预期的，是由高度有序的水分子返回到本体溶液而产生的。然而，有利的熵项被相对较大的不利焓项所抵消。通过比较结合过程中氢键和溶剂化变化的程度，使这一观察结果合理化。有人提出，通过水分子的间接相互作用将提供更大数量的氢键在复杂的具有更高的占有率比在本体溶液中，从而稳定的复杂。
The interactions of trimannosides 1 and 2 with Con A were studied to reveal the effects of displacement of well-ordered water molecules on the thermodynamic parameters of protein-ligand complexation. Trisaccharide 2 is a derivative of 1. in which the hydroxyl at C-2 of the central mannose unit is replaced by a hydroxyethyl moiety. Upon binding, this moiety displaces a conserved water molecule present in the Con A binding site. Structural studies by NMR spectroscopy and MD simulations showed that the two compounds have very similar solution conformational properties. MD simulations of the complexes of Con A with 1 and 2 demonstrated that the hydroxyethyl side chain of 2 can establish the same hydrogen bonds in a low energy conformation with the protein binding site as those mediated by the water molecule in the complex of 1 with Con A. Isothermal titration microcalorimetry (ITC) measurements showed that 2 has a more favorable entropy of binding compared to 1. This term, which was expected, arises from the return of the highly ordered water molecule to bulk solution. The favorable entropy term was, however, offset by a relatively large unfavorable enthalpy term. This observation was rationalized by comparing the extent of hydrogen bond and solvation changes during binding. It is proposed that an indirect interaction through a water molecule will provide a larger number of hydrogen bonds in the complex that have higher occupancies than in bulk solution, thereby stabilizing the complex.