Key interactions in antibody recognition of synthetic sweeteners: Crystal structures of NC6.8 Fab co-crystallized with high potency sweetener compound SC45647 and with TES.
Year: 2005
Type: article
Abstract: The complex crystal structures of the murine monoclonal IgG2b(?) antibody NC6.8 Fab fragment complexed with high-potency sweetener compound (SC45647) and non tasting high affinity antagonist TES have been determined.A comparative analysis with the structure of NC6.8 complexed with the super-potency sweetener NC174 reveals that the zwitterionic, tri-substituted guanidinium sweeteners as well as the zwitterionic antagonist TES interact with the same residues in the antigen binding pocket of NC6.8.In case of the nonsweetener TES, the interactions are largely ind irectly mediated through a hydrogen bonded water network.The presence of a hydrophobic moiety as a major determinant for sweet taste has been confirmed, and its nature is likely a discriminator for super-versus high-potency sweeteners.Neither high-potency sweetener SC45657 nor non-sweet tasting TES induce any significant change in the NC6.8 Fab elbow angle, which excludes the necessity of ligand-induced allostery as a general requirement for ligand binding in NC6.8.A conserved water molecule mediating hydrogen binding to residues buried in the antigen binding pocket has been observed in all three NC6.8 complexes.Since the antigen binding pocket of NC6.8 can adopt to multiple ligandsincluding high affinity antagonists -it is important that structure guided sweetener design based on available complexes fully considers the exceptional structural adaptability of receptormimicking antibody models.
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W251877977