CH-π Interactions in Glycan Recognition

Carbohydrate recognition is crucial for biological processes ranging from development to immune system function to host-pathogen interactions. The proteins that bind glycans are faced with a daunting task: to coax these hydrophilic species out of water and into a binding site. Here, we examine the forces underlying glycan recognition by proteins. Our previous bioinformatic study of glycan-binding sites indicated that the most overrepresented side chains are electron-rich aromatic residues, including tyrosine and tryptophan. These findings point to the importance of CH-pi interactions for glycan binding. Studies of CH-pi. interactions show a strong dependence on the presence of an electron-rich pi system, and the data indicate binding is enhanced by complementary electronic interactions between the electron-rich aromatic ring and the partial positive charge of the carbohydrate C-H protons. This electronic dependence means that carbohydrate residues with multiple aligned highly polarized C-H bonds, such as beta-galactose, form strong CH-pi interactions, whereas less polarized residues such as alpha-mannose do not. This information can guide the design of proteins to recognize sugars and the generation of ligands for proteins, small molecules, or catalysts that bind sugars.

Automated summary

The text discusses how proteins recognize sugars through CH-π interactions, highlighting the importance of electron-rich aromatic residues in glycan binding.