title: Conformational and molecular modeling studies of sulfated cholecystokinin-15.
abstract: Conformational features of the C-terminal carboxyamidated pentadecapeptide of CCK (S(19)HRISDRD[SO(4)]-YMGWMDF(33)-NH(2)) were determined by NMR spectroscopy in a zwitterionic membrane-mimetic solvent system, composed of DPC micelles. The C-terminal octapeptide consisted of a well-defined pseudohelix that was nearly identical to the structure previously reported for nonsulfated CCK-8 in the same solvent system. N-terminal amino acids of CCK-15 were highly disordered, with no clear conformational preference. Extensive NOE-restrained molecular dynamics simulations of the CCK-15/CCK(1)-R complex suggested that almost all the experimentally determined intermolecular contact points provided by NMR, site-directed mutagenesis, and photoaffinity labeling could be simultaneously satisfied, when the N-terminus of the ligand is placed in close spatial proximity to the N-terminus of the receptor.
authors.affiliation: Department of Chemistry, Division of Biology & Medicine, Brown University, Providence, RI 02912, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Giragossian
authors.forename: Shane
authors.initials: S
authors.lastname: Stone
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Papini
authors.forename: Luis
authors.initials: L
authors.lastname: Moroder
authors.forename: Dale F
authors.initials: DF
authors.lastname: Mierke
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002766:Cholecystokinin / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry; D011487:Protein Conformation; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000737:chemistry / Q000378:metabolism
chemical_list: C448625:CCK 15; D008823:Micelles; D010446:Peptide Fragments; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; C457776:sulfated cholecystokinin 15; D010767:Phosphorylcholine; C028810:dodecylphosphocholine; D002766:Cholecystokinin