title: Relationships between molecular structure and perceived odor quality of ligands for a human olfactory receptor.
abstract: Perception of thousands of odors by a few hundreds of olfactory receptors (ORs) results from a combinatorial coding, in which one OR recognizes multiple odorants and an odorant is recognized by a specific group of ORs. Moreover, odorants could act both as agonists or antagonists depending on the OR. This dual agonist-antagonist combinatorial coding is in good agreement with behavioral and psychophysical observations of mixture perception. We previously described the odorant repertoire of a human OR, OR1G1, identifying both agonists and antagonists. In this paper, we performed a 3D-quantitative structure-activity relationship (3D-QSAR) study of these ligands. We obtained a double-alignment model explaining previously reported experimental activities and permitting to predict novel agonists and antagonists for OR1G1. These model predictions were experimentally validated. Thereafter, we evaluated the statistical link between OR1G1 response to odorants, 3D-QSAR categorization of OR1G1 ligands, and their olfactory description. We demonstrated that OR1G1 recognizes a group of odorants that share both 3D structural and perceptual qualities. We hypothesized that OR1G1 contributes to the coding of waxy, fatty, and rose odors in humans.
authors.affiliation: Institut National de la Recherche Agronomique, Unité Minte de Recherche 1197 Neurobiologie de l'Olfaction et de la Prise Alimentaire, F-78352 Jouy-en-Josas, France. guenhael.sanz@jouy.inra.fr
authors.forename: Guenhaël
authors.initials: G
authors.lastname: Sanz
authors.forename: Thierry
authors.initials: T
authors.lastname: Thomas-Danguin
authors.forename: El Hassan
authors.initials: el H
authors.lastname: Hamdani
authors.forename: Claire
authors.initials: C
authors.lastname: Le Poupon
authors.forename: Loïc
authors.initials: L
authors.lastname: Briand
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Pernollet
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Guichard
authors.forename: Anne
authors.initials: A
authors.lastname: Tromelin
mesh_terms: D002460:Cell Line; D003627:Data Interpretation, Statistical; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009812:Odorants / Q000032:analysis; D017434:Protein Structure, Tertiary; D018035:Receptors, Odorant / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; C533784:OR1G1 protein, human; D018035:Receptors, Odorant