Characterization of the beta-D-glucopyranoside binding site of the human bitter taste receptor hTAS2R16.
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.
Sakurai
Takanobu
T
General Research Institute of Food Science and Technology, Nissin Foods Holdings Co., Ltd., Shiga 525-0058, Japan.
Misaka
Takumi
T
Ishiguro
Masaji
M
Masuda
Katsuyoshi
K
Sugawara
Taishi
T
Ito
Keisuke
K
Kobayashi
Takuya
T
Matsuo
Shinji
S
Ishimaru
Yoshiro
Y
Asakura
Tomiko
T
Abe
Keiko
K
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
D001592:Benzyl Alcohols; D005960:Glucosides; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; C005696:salicin