On the importance of carbohydrate-aromatic interactions for the molecular recognition of oligosaccharides by proteins: NMR studies of the structure and binding affinity of AcAMP2-like peptides with non-natural naphthyl and fluoroaromatic residues
On the importance of carbohydrate-aromatic interactions for the molecular recognition of oligosaccharides by proteins: NMR studies of the structure and binding affinity of AcAMP2-like peptides with non-natural naphthyl and fluoroaromatic residues
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DOI：
10.1002/chem.200500367
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发表时间：
2005-11-18
影响因子：
4.3
通讯作者：
Jiménez-Barbero, J
中科院分区：
文献类型：
--
作者：
Chávez, MI;Andreu, C;Jiménez-Barbero, J
通过核磁共振光谱研究了各种修饰的hevein结构域与壳低聚糖的特异性相互作用，以评估芳香族-碳水化合物相互作用对于中性糖分子识别的重要性。这些突变的AcAMP 2-样肽，其中有4-氟-苯丙氨酸，色氨酸，或2-萘基丙氨酸在关键的相互作用的位置，已通过固相合成制备。它们的三维结构，当绑定到几丁质衍生的三糖，已推导出由NMR光谱。利用DYANA软件和AMBER5.0力场下的约束分子动力学模拟，得到了蛋白质-糖复合物的三维结构。热力学分析的相互作用时发生的复杂的形成也进行了。关于结合亲和力，所获得的数据允许推断，芳香基团越大，缔合常数和结合焓越高。在所有情况下，熵都反对束缚。相反，通过连接氟原子使芳环失活降低了结合亲和力，伴随着焓的降低。因此，已经评估了芳香环的化学性质对于建立糖接触的作用。
The specific interaction of a variety of modified hevein domains to chitooligosaccharides has been studied by NMR spectroscopy in order to assess the importance of aromatic-carbohydrate interactions for the molecular recognition of neutral sugars. These mutant AcAMP2-like peptides, which have 4-fluoro-phenylalanine, tryptophan, or 2-naphthylalanine at the key interacting positions, have been prepared by solid-phase synthesis. Their three-dimensional structures, when bound to the chitin-derived trisaccharide, have been deduced by NMR spectroscopy. By using DYANA and restrained molecular dynamics simulations with the AMBER 5.0 force field, the three-dimensional structures of the protein-sugar complexes have been obtained. The thermodynamic analysis of the interactions that occur upon complex formation have also been carried out. Regarding binding affinity, the obtained data have permitted the deduction that the larger the aromatic group, the hi-her the association constant and the binding enthalpy. In all cases, entropy opposes binding. In contrast, deactivation of the aromatic rings by attaching fluorine atoms decreases the binding affinity, with a concomitant decrease in enthalpy. The role of the chemical nature of the aromatic ring for establishing sugar contacts has been thus evaluated.