Molecular mechanism of the sweet taste enhancers

• DOI: 10.1073/pnas.0911660107
• Publication Date: 2010-02-20T03:02:36Z
• Authors: Feng Zhang; Boris Klebansky; Richard M. Fine; Haitian Liu; Hong Xu; Guy Servant; Mark Zoller; Catherine Tachdjian; Xiaodong Li
• Keywords: Models, Molecular; Sucrose; 0303 health sciences; Binding Sites; Dose-Response Relationship, Drug; Sequence Homology, Amino Acid; Molecular Sequence Data; Transfection; Cell Line; Protein Structure, Tertiary; Rats; Receptors, G-Protein-Coupled; 03 medical and health sciences; Allosteric Regulation; Sweetening Agents; Mutation; Animals; Humans; Amino Acid Sequence; Protein Binding

Positive allosteric modulators of the human sweet taste receptor have been developed as a new way of reducing dietary sugar intake. Besides their potential health benefit, the sweet taste enhancers are also valuable tool molecules to study the general mechanism of positive allosteric modulations of T1R taste receptors. Using chimeric receptors, mutagenesis, and molecular modeling, we reveal how these sweet enhancers work at the molecular level. Our data argue that the sweet enhancers follow a similar mechanism as the natural umami taste enhancer molecules. Whereas the sweeteners bind to the hinge region and induce the closure of the Venus flytrap domain of T1R2, the enhancers bind close to the opening and further stabilize the closed and active conformation of the receptor.