Carbohydrate鈥揂romatic Interactions in Proteins
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- 作者：Kieran L. Hudson ; Gail J. Bartlett ; Roger C. Diehl ; Jon Agirre ; Timothy Gallagher ; Laura L. Kiessling ; Derek N. Woolfson
- 刊名：Journal of the American Chemical Society
- 出版年：2015
- 出版时间：December 9, 2015
- 年：2015
- 卷：137
- 期：48
- 页码：15152-15160
- 全文大小：587K
- ISSN：1520-5126
文摘
Protein鈥揷arbohydrate 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鈥揌 bonds interact preferentially with aromatic residues. These preferences are consistent with the electronic properties of both the carbohydrate C鈥揌 bonds and the aromatic residues. Those carbohydrates that present patches of electropositive saccharide C鈥揌 bonds engage more often in CH鈭捪€ interactions involving electron-rich aromatic partners. These electronic effects are also manifested when carbohydrate鈥揳romatic interactions are monitored in solution: NMR analysis indicates that indole favorably binds to electron-poor C鈥揌 bonds of model carbohydrates, and a clear linear free energy relationships with substituted indoles supports the importance of complementary electronic effects in driving protein鈥揷arbohydrate interactions. Together, our data indicate that electrostatic and electronic complementarity between carbohydrates and aromatic residues play key roles in driving protein鈥揷arbohydrate complexation. Moreover, these weak noncovalent interactions influence which saccharide residues bind to proteins, and how they are positioned within carbohydrate-binding sites.