title: Aldehyde recognition and discrimination by mammalian odorant receptors via functional group-specific hydration chemistry.
abstract: The mammalian odorant receptors (ORs) form a chemical-detecting interface between the atmosphere and the nervous system. This large gene family is composed of hundreds of membrane proteins predicted to form as many unique small molecule binding niches within their G-protein coupled receptor (GPCR) framework, but very little is known about the molecular recognition strategies they use to bind and discriminate between small molecule odorants. Using rationally designed synthetic analogs of a typical aliphatic aldehyde, we report evidence that among the ORs showing specificity for the aldehyde functional group, a significant percentage detect the aldehyde through its ability to react with water to form a 1,1-geminal (gem)-diol. Evidence is presented indicating that the rat OR-I7, an often-studied and modeled OR known to require the aldehyde function of octanal for activation, is likely one of the gem-diol activated receptors. A homology model based on an activated GPCR X-ray structure provides a structural hypothesis for activation of OR-I7 by the gem-diol of octanal.
authors.affiliation: Department of Chemistry, The City College of New York, and Biochemistry Program, The City University of New York Graduate Center , New York, New York 10031, United States.
authors.forename: Yadi
authors.initials: Y
authors.lastname: Li
authors.forename: Zita
authors.initials: Z
authors.lastname: Peterlin
authors.forename: Jianghai
authors.initials: J
authors.lastname: Ho
authors.forename: Tali
authors.initials: T
authors.lastname: Yarnitzky
authors.forename: Min Ting
authors.initials: MT
authors.lastname: Liu
authors.forename: Merav
authors.initials: M
authors.lastname: Fichman
authors.forename: Masha Y
authors.initials: MY
authors.lastname: Niv
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsunami
authors.forename: Stuart
authors.initials: S
authors.lastname: Firestein
authors.forename: Kevin
authors.initials: K
authors.lastname: Ryan
mesh_terms: D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D051381:Rats; D018035:Receptors, Odorant / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D018035:Receptors, Odorant