title: Molecular mechanism of the sweet taste enhancers.
abstract: 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.
authors.affiliation: Senomyx, Inc, San Diego, CA 92121, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Boris
authors.initials: B
authors.lastname: Klebansky
authors.forename: Richard M
authors.initials: RM
authors.lastname: Fine
authors.forename: Haitian
authors.initials: H
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Guy
authors.initials: G
authors.lastname: Servant
authors.forename: Mark
authors.initials: M
authors.lastname: Zoller
authors.forename: Catherine
authors.initials: C
authors.lastname: Tachdjian
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013395:Sucrose / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D013549:Sweetening Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection
chemical_list: D043562:Receptors, G-Protein-Coupled; D013549:Sweetening Agents; C431926:taste receptors, type 1; D013395:Sucrose; C026285:trichlorosucrose