title: Analysis of the molecular basis for octanal interactions in the expressed rat 17 olfactory receptor.
abstract: Expression studies have shown that the rat I7 olfactory receptor (OR-I7) responds preferentially to the aldehyde n-octanal. We wished to predict which residues in OR-I7 bind octanal and how the biophysical properties of these residues determine the receptor's odor selectivity. Building on our previous work on aldehyde interactions in olfactory receptors, we constructed a molecular model of OR-I7 based on the 7.5 A resolution three-dimensional map of rhodopsin. Octanal was automatically docked in the model. The results predicted an odor-binding pocket approximately 10 A from the extracellular surface, in a location similar to the epinephrine-binding pocket of the beta-adrenergic receptor and the odor-binding pocket of a previous olfactory receptor model. A lysine on TM4 and an aspartate on TM5 interacted with the aldehyde moiety of octanal. Hydrophobic residues formed Van der Waals contacts with the hydrocarbon portion of octanal. We docked related odor compounds and found that the predicted affinities compared favorably with experimental results. We also tested a number of amino acid substitutions in order to predict their effects on octanal affinity and provide leads for future experimental work.
authors.affiliation: Section of Neurobiology and Center for Medical Informatics, Yale University School of Medicine, New Haven, CT 06520, USA. mike@habibi.med.yale.edu
authors.forename: M S
authors.initials: MS
authors.lastname: Singer
mesh_terms: D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D008024:Ligands; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D051381:Rats; D018035:Receptors, Odorant / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012243:Rhodopsin / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000447:Aldehydes; D008024:Ligands; D018035:Receptors, Odorant; D001224:Aspartic Acid; D012243:Rhodopsin; D008239:Lysine; C031639:caprylic aldehyde