title: Characterization of the beta-D-glucopyranoside binding site of the human bitter taste receptor hTAS2R16.
abstract: G-protein-coupled receptors mediate the senses of taste, smell, and vision in mammals. Humans recognize thousands of compounds as bitter, and this response is mediated by the hTAS2R family, which is one of the G-protein-coupled receptors composed of only 25 receptors. However, structural information on these receptors is limited. To address the molecular basis of bitter tastant discrimination by the hTAS2Rs, we performed ligand docking simulation and functional analysis using a series of point mutants of hTAS2R16 to identify its binding sites. The docking simulation predicted two candidate binding structures for a salicin-hTAS2R16 complex, and at least seven amino acid residues in transmembrane 3 (TM3), TM5, and TM6 were shown to be involved in ligand recognition. We also identified the probable salicin-hTAS2R16 binding mode using a mutated receptor experiment. This study characterizes the molecular interaction between hTAS2R16 and beta-D-glucopyranoside and will also facilitate rational design of bitter blockers.
authors.affiliation: General Research Institute of Food Science and Technology, Nissin Foods Holdings Co., Ltd., Shiga 525-0058, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Sakurai
authors.forename: Takumi
authors.initials: T
authors.lastname: Misaka
authors.forename: Masaji
authors.initials: M
authors.lastname: Ishiguro
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Masuda
authors.forename: Taishi
authors.initials: T
authors.lastname: Sugawara
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ito
authors.forename: Takuya
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsuo
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Ishimaru
authors.forename: Tomiko
authors.initials: T
authors.lastname: Asakura
authors.forename: Keiko
authors.initials: K
authors.lastname: Abe
mesh_terms: D001592:Benzyl Alcohols / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D005960:Glucosides / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D000098706:Taste Receptors, Type 2
chemical_list: D001592:Benzyl Alcohols; D005960:Glucosides; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; C005696:salicin