Conformational analysis of human calcitonin in solution

✍ Scribed by Kiyoshi Ogawa; Shigenori Nishimura; Masamitsu Doi; Hiroyuki Takashima; Yoshinori Nishi; Takuya Yoshida; Tadayasu Ohkubo; Yuji Kobayashi

• Book ID: 105360505
• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 302 KB
• Volume: 12
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.687

✦ Synopsis

Abstract

The solution conformation of human calcitonin in a mixture of 60% water and 40% trifluoroethanol has been determined by the combined use of ^1^H NMR spectroscopy and distance geometry calculations with a distributed computing technique. ^1^H 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 Asn^3^—Phe^22^. The conformation is characterized by a nearly amphiphilic α‐helix domain that extends from Leu^4^ in the cyclic region to His^20^. 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, Tyr^12^, Phe^16^ and Phe^19^, 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.