title: Conformational analysis of human calcitonin in solution.
abstract: The solution conformation of human calcitonin in a mixture of 60% water and 40% trifluoroethanol has been determined by the combined use of 1H NMR spectroscopy and distance geometry calculations with a distributed computing technique. 1H NMR spectroscopy provided 195 distance constraints and 13 hydrogen bond constraints. The 20 best converged structures exhibit atomic rmsd of 0.43 A for the backbone atoms from the averaged coordinate position in the region of Asn3-Phe22. The conformation is characterized by a nearly amphiphilic alpha-helix domain that extends from Leu4 in the cyclic region to His20. There are no significant differences observed among the overall structures of a series of calcitonins obtained from ultimobranchial bodies, including those that possess 20- to 50-fold greater activity. Three aromatic amino acid residues, Tyr12, Phe16 and Phe19, form a hydrophobic surface of human calcitonin. Bulky side chains on the surface could interfere with the ligand-receptor interaction thereby causing its low activity, relative to those of other species.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, 565-0871 Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ogawa
authors.forename: Shigenori
authors.initials: S
authors.lastname: Nishimura
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Doi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takashima
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nishi
authors.forename: Takuya
authors.initials: T
authors.lastname: Yoshida
authors.forename: Tadayasu
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D002116:Calcitonin / Q000737:chemistry*; D004524:Eels; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods / Q000592:standards; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012015:Reference Standards; D012474:Salmon; D012996:Solutions / Q000737:chemistry
chemical_list: D012996:Solutions; D002116:Calcitonin