Conformational analysis of human calcitonin in solution.
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.
Ogawa
Kiyoshi
K
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, 565-0871 Japan.
Nishimura
Shigenori
S
Doi
Masamitsu
M
Takashima
Hiroyuki
H
Nishi
Yoshinori
Y
Yoshida
Takuya
T
Ohkubo
Tadayasu
T
Kobayashi
Yuji
Y
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
D012996:Solutions; D002116:Calcitonin