Carbohydrate-Aromatic Interactions in Proteins.
Carbohydrate-Aromatic Interactions in Proteins.
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DOI：
10.1021/jacs.5b08424
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发表时间：
2015-12-09
影响因子：
15
通讯作者：
Woolfson DN
中科院分区：
文献类型：
--
作者：
Hudson KL;Bartlett GJ;Diehl RC;Agirre J;Gallagher T;Kiessling LL;Woolfson DN
蛋白质-碳水化合物相互作用在健康和疾病中起着关键作用。然而，定义和操纵这些相互作用一直受到阻碍的基本力量的不完整的理解。为了阐明碳水化合物识别中的共同和区别特征，我们定量分析了具有非共价结合碳水化合物的蛋白质的X射线晶体结构。在碳水化合物结合口袋内，脂肪族疏水残基是不利的，而芳香族侧链富集。最大的偏好是色氨酸，患病率增加9倍。不同单糖周围氨基酸的空间取向的变化表明特定的碳水化合物C-H键优先与芳香残基相互作用。这些偏好与碳水化合物C-H键和芳香残基的电子性质一致。那些呈现正电糖C-H键的碳水化合物更经常参与CH−π相互作用，涉及富电子芳香族伴侣。当在溶液中监测碳水化合物-芳香族相互作用时，这些电子效应也表现出来：NMR分析表明，吲哚有利地与模型碳水化合物的贫电子C-H键结合，并且与取代吲哚的明确线性自由能关系支持互补电子效应在驱动蛋白质-碳水化合物相互作用中的重要性。总之，我们的数据表明，碳水化合物和芳香族残基之间的静电和电子互补性在驱动蛋白质-碳水化合物络合中起着关键作用。此外，这些弱的非共价相互作用影响哪些糖残基与蛋白质结合，以及它们如何定位在碳水化合物结合位点内。
Protein–carbohydrate interactions play pivotal roles in health and disease. However, defining and manipulating these interactions has been hindered by an incomplete understanding of the underlying fundamental forces. To elucidate common and discriminating features in carbohydrate recognition, we have analyzed quantitatively X-ray crystal structures of proteins with noncovalently bound carbohydrates. Within the carbohydrate-binding pockets, aliphatic hydrophobic residues are disfavored, whereas aromatic side chains are enriched. The greatest preference is for tryptophan with an increased prevalence of 9-fold. Variations in the spatial orientation of amino acids around different monosaccharides indicate specific carbohydrate C–H bonds interact preferentially with aromatic residues. These preferences are consistent with the electronic properties of both the carbohydrate C–H bonds and the aromatic residues. Those carbohydrates that present patches of electropositive saccharide C–H bonds engage more often in CH−π interactions involving electron-rich aromatic partners. These electronic effects are also manifested when carbohydrate–aromatic interactions are monitored in solution: NMR analysis indicates that indole favorably binds to electron-poor C–H bonds of model carbohydrates, and a clear linear free energy relationships with substituted indoles supports the importance of complementary electronic effects in driving protein–carbohydrate interactions. Together, our data indicate that electrostatic and electronic complementarity between carbohydrates and aromatic residues play key roles in driving protein–carbohydrate complexation. Moreover, these weak noncovalent interactions influence which saccharide residues bind to proteins, and how they are positioned within carbohydrate-binding sites.