title: Structure of cholecystokinin receptor binding sites and mechanism of activation/inactivation by agonists/antagonists.
abstract: Delineation of CCK receptor binding sites is a prerequisite for the understanding of the molecular basis for ligand recognition, partial agonism, ligand-induced traffiking of receptor signalling. In the current paper, we illustrate how, in the past 5 years, studies from our laboratory and others have provided new data on the molecular basis of the pharmacology and functioning of CCK1 and CCK2 receptors. Available data on CCK1 and CCK2R binding sites indicate that 1) homologous regions of the two receptors are involved in the binding site of CCK, however, positioning of CCK slightly differs; 2) binding sites of non-peptide agonists/antagonist are buried in the pocket formed by transmembrane helices and overlap that of CCK and 3) residues of the binding sites as well as of conserved motifs such as E/DRY, NPXXY are crucial for receptor activation.
authors.affiliation: INSERM U 531, Louis Bugnard Institute, CHU Rangueil, Bat. L3, 31403 Toulouse Cedex 4, France. Daniel.Fourmy@toulouse.inserm.fr
authors.forename: Daniel
authors.initials: D
authors.lastname: Fourmy
authors.forename: Chantal
authors.initials: C
authors.lastname: Escrieut
authors.forename: Elodie
authors.initials: E
authors.lastname: Archer
authors.forename: Céline
authors.initials: C
authors.lastname: Galès
authors.forename: Véronique
authors.initials: V
authors.lastname: Gigoux
authors.forename: Bernard
authors.initials: B
authors.lastname: Maigret
authors.forename: Luis
authors.initials: L
authors.lastname: Moroder
authors.forename: Sandrine
authors.initials: S
authors.lastname: Silvente-Poirot
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
authors.forename: Jean-Alain
authors.initials: JA
authors.lastname: Fehrentz
authors.forename: Lucien
authors.initials: L
authors.lastname: Pradayrol
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002766:Cholecystokinin / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin