Ogawa Kiyoshi, Nishimura Shigenori, Doi Masamitsu, Takashima Hiroyuki, Nishi Yoshinori, Yoshida Takuya, Ohkubo Tadayasu, Kobayashi Yuji
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, 565-0871 Japan.
J Pept Sci. 2006 Jan;12(1):51-7. 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 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.
通过结合使用¹H NMR光谱法以及采用分布式计算技术的距离几何计算法，已确定人降钙素在60%水和40%三氟乙醇混合物中的溶液构象。¹H NMR光谱法提供了195个距离约束和13个氢键约束。20个收敛性最佳的结构在Asn3 - Phe22区域内，主链原子相对于平均坐标位置的原子均方根偏差为0.43 Å。该构象的特征是一个近乎两亲性的α - 螺旋结构域，从环状区域的Leu4延伸至His20。从后鳃体获得的一系列降钙素的整体结构之间未观察到显著差异，包括那些活性高20至50倍的降钙素。三个芳香族氨基酸残基Tyr12、Phe16和Phe19形成了人降钙素的疏水表面。相对于其他物种的降钙素，表面上较大的侧链可能会干扰配体 - 受体相互作用，从而导致其活性较低。
