title: The Dependence of Carbohydrate-Aromatic Interaction Strengths on the Structure of the Carbohydrate.
abstract: Interactions between proteins and carbohydrates are ubiquitous in biology. Therefore, understanding the factors that determine their affinity and selectivity are correspondingly important. Herein, we have determined the relative strengths of intramolecular interactions between a series of monosaccharides and an aromatic ring close to the glycosylation site in an N-glycoprotein host. We employed the enhanced aromatic sequon, a structural motif found in the reverse turns of some N-glycoproteins, to facilitate face-to-face monosaccharide-aromatic interactions. A protein host was used because the dependence of the folding energetics on the identity of the monosaccharide can be accurately measured to assess the strength of the carbohydrate-aromatic interaction. Our data demonstrate that the carbohydrate-aromatic interaction strengths are moderately affected by changes in the stereochemistry and identity of the substituents on the pyranose rings of the sugars. Galactose seems to make the weakest and allose the strongest sugar-aromatic interactions, with glucose, N-acetylglucosamine (GlcNAc) and mannose in between. The NMR solution structures of several of the monosaccharide-containing N-glycoproteins were solved to further understand the origins of the similarities and differences between the monosaccharide-aromatic interaction energies. Peracetylation of the monosaccharides substantially increases the strength of the sugar-aromatic interaction in the context of our N-glycoprotein host. Finally, we discuss our results in light of recent literature regarding the contribution of electrostatics to CH-π interactions and speculate on what our observations imply about the absolute conservation of GlcNAc as the monosaccharide through which N-linked glycans are attached to glycoproteins in eukaryotes.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute , La Jolla, California 92037, United States.|Department of Chemistry, The Scripps Research Institute , La Jolla, California 92037, United States.
authors.forename: Che-Hsiung
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute , La Jolla, California 92037, United States.
authors.forename: Sangho
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute , La Jolla, California 92037, United States.
authors.forename: David E
authors.initials: DE
authors.lastname: Mortenson
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia , 315 Riverbend Road, Athens, Georgia 30602, United States.
authors.forename: B Lachele
authors.initials: BL
authors.lastname: Foley
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia , 315 Riverbend Road, Athens, Georgia 30602, United States.
authors.forename: Xiaocong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia , 315 Riverbend Road, Athens, Georgia 30602, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Woods
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers University , Piscataway, New Jersey 08854, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Case
authors.affiliation: Department of Chemistry, The Scripps Research Institute , La Jolla, California 92037, United States.
authors.forename: Evan T
authors.initials: ET
authors.lastname: Powers
authors.affiliation: Department of Chemistry, The Scripps Research Institute , La Jolla, California 92037, United States.|Genomics Research Center, Academia Sinica , Taipei 115, Taiwan.|The Skaggs Institute for Chemical Biology , La Jolla, California 92037, United States.
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute , La Jolla, California 92037, United States.
authors.forename: H Jane
authors.initials: HJ
authors.lastname: Dyson
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute , La Jolla, California 92037, United States.|Department of Chemistry, The Scripps Research Institute , La Jolla, California 92037, United States.|The Skaggs Institute for Chemical Biology , La Jolla, California 92037, United States.
authors.forename: Jeffery W
authors.initials: JW
authors.lastname: Kelly
mesh_terms: D006023:Glycoproteins / Q000737:chemistry*; D006031:Glycosylation; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009005:Monosaccharides / Q000737:chemistry*; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D006023:Glycoproteins; D006841:Hydrocarbons, Aromatic; D009005:Monosaccharides