Falcigno L, Paolillo L, D'Auria G, Saviano M, Simonetti M, Di Bello C
Department of Chemistry, University of Naples, Italy.
Biopolymers. 1996 Dec;39(6):837-48. doi: 10.1002/(SICI)1097-0282(199612)39:6%3C837::AID-BIP8%3E3.0.CO;2-W.
The combined use of several nuclear magnetic resonance and restrained molecular dynamics techniques allowed the formulation of a molecular model for the preferred solution conformation of a synthetic peptide reproducing the [1-20] processing domain of the pro-ocytocin-neurophysin precursor. In the model, the conformation of the 20-membered tocin ring, with the two Cys1 and Cys6 residues bridged by a disulphide bond, is very close to that observed for isolated ocytocin in the solid state; in addition, a type II beta-turn is postulated for the 7-10 segment of the acyclic tail containing the Lys11-Arg12 processing site, and connecting ocytocin to the neurophysin domain, while the C-terminal 13-20 segment of the molecule is believed to assume a helical structure. This particular structural organization could be important in participating as the favorable conformation for optimal substrate-enzyme active site recognition and processing by specific endoproteases.
结合使用多种核磁共振和受限分子动力学技术，得以构建一个分子模型，用于模拟一种合成肽的优选溶液构象，该合成肽再现了促催产素-神经垂体素前体的[1-20]加工结构域。在该模型中，由二硫键桥接两个半胱氨酸1和半胱氨酸6残基的20元催产素环的构象，与固态下分离的催产素所观察到的构象非常接近；此外，对于包含赖氨酸11-精氨酸12加工位点的无环尾部的7-10片段，假定存在一个II型β-转角，该片段将催产素与神经垂体素结构域相连，而分子的C端13-20片段据信呈现螺旋结构。这种特殊的结构组织可能作为最佳底物-酶活性位点识别和特定内切蛋白酶加工的有利构象参与其中，因而具有重要意义。
