title: Modeling the human PTC bitter-taste receptor interactions with bitter tastants.
abstract: We employed the first principles computational method MembStruk and homology modeling techniques to predict the 3D structures of the human phenylthiocarbamide (PTC) taste receptor. This protein is a seven-transmembrane-domain G protein-coupled receptor that exists in two main forms worldwide, designated taster and nontaster, which differ from each other at three amino-acid positions. 3D models were generated with and without structural similarity comparison to bovine rhodopsin. We used computational tools (HierDock and ScanBindSite) to generate models of the receptor bound to PTC ligand to estimate binding sites and binding energies. In these models, PTC binds at a site distant from the variant amino acids, and PTC binding energy was equivalent for both the taster and nontaster forms of the protein. These models suggest that the inability of humans to taste PTC is due to a failure of G protein activation rather than decreased binding affinity of the receptor for PTC. Amino-acid substitutions in the sixth and seventh transmembrane domains of the nontaster form of the protein may produce increased steric hindrance between these two alpha-helices and reduce the motion of the sixth helix required for G protein activation.
authors.affiliation: Biological Sciences Department, California State Polytechnic University Pomona, Pomona, CA 91768, USA.
authors.forename: Wely B
authors.initials: WB
authors.lastname: Floriano
authors.forename: Spencer
authors.initials: S
authors.lastname: Hall
authors.forename: Nagarajan
authors.initials: N
authors.lastname: Vaidehi
authors.forename: Unkyung
authors.initials: U
authors.lastname: Kim
authors.forename: Dennis
authors.initials: D
authors.lastname: Drayna
authors.forename: William A
authors.initials: WA
authors.lastname: Goddard
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002417:Cattle; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D012243:Rhodopsin / Q000737:chemistry; D040681:Structural Homology, Protein; D013649:Taste; D000098706:Taste Receptors, Type 2
chemical_list: D008024:Ligands; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D012243:Rhodopsin; D019204:GTP-Binding Proteins