Conformational analysis of human calcitonin in solution

• Published in: Journal of peptide science Vol. 12; no. 1; pp. 51 - 57
• Main Authors: Ogawa, Kiyoshi, Nishimura, Shigenori, Doi, Masamitsu, Takashima, Hiroyuki, Nishi, Yoshinori, Yoshida, Takuya, Ohkubo, Tadayasu, Kobayashi, Yuji
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-01-2006
• Subjects: amphiphilic α-helix; Animals; calcitonin; Calcitonin - chemistry; eel calcitonin; Eels; human calcitonin; Humans; Magnetic Resonance Spectroscopy - methods; Magnetic Resonance Spectroscopy - standards; Models, Molecular; NMR; Protein Conformation; Protein Structure, Secondary; Reference Standards; Salmon; Solutions - chemistry
• ISSN: 1075-2617; 1099-1387
• DOI: 10.1002/psc.687

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 Å for the backbone atoms from the averaged coordinate position in the region of Asn3—Phe22. The conformation is characterized by a nearly amphiphilic α‐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. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.