A single lysyl residue defines the binding specificity of a human odorant-binding protein for aldehydes.
Odorant-binding proteins (OBPs) are small abundant soluble proteins belonging to the lipocalin superfamily, which are thought to carry hydrophobic odorants through aqueous mucus towards olfactory receptors. Human variant hOBP-2A has been demonstrated to bind numerous odorants of different chemical classes with a higher affinity for aldehydes and fatty acids. Three lysyl residues of the binding pocket (Lys62, Lys82 and Lys112) have been suggested as candidates for playing such a role. Here, using site-directed mutagenesis and fluorescent probe displacements, we show that Lys112 is the major determinant for governing hOBP-2A specificity towards aldehydes and small carboxylic acids.
Biochimie de l'olfaction et de la gustation, Neurobiologie de l'Olfaction et de la Prise Alimentaire, UMR 1197 - INRA-Université Paris XI, INRA, Domaine de vilvert, Bâtiment 526, F 78352 Jouy-en-Josas Cedex, France.
Lionel
L
Tcatchoff
Claude
C
Nespoulous
Jean-Claude
JC
Pernollet
Loïc
L
Briand
D015057:1-Naphthylamine / Q000031:analogs & derivatives; D000447:Aldehydes / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D003619:Dansyl Compounds; D005227:Fatty Acids; D005456:Fluorescent Dyes; D006801:Humans; D008024:Ligands; D054834:Lipocalins; D008239:Lysine / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics; D019308:Palmitic Acid / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D017385:Sequence Homology; D013379:Substrate Specificity; D017186:Titrimetry
D000447:Aldehydes; D002352:Carrier Proteins; D003619:Dansyl Compounds; D005227:Fatty Acids; D005456:Fluorescent Dyes; D008024:Ligands; D054834:Lipocalins; C509994:OBP2A protein, human; D011994:Recombinant Proteins; D019308:Palmitic Acid; C054400:11-(dansylamino)undecanoic acid; C005444:N-phenyl-1-naphthylamine; D015057:1-Naphthylamine; C479548:undecanal; D008239:Lysine