Bhaskaran R, Yu C
Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
Int J Pept Protein Res. 1994 Apr;43(4):393-401. doi: 10.1111/j.1399-3011.1994.tb00536.x.
The conformation of viroisin, the monocyclic toxic heptapeptide of the virotoxin family from mushroom Amanita virosa, was analysed using two-dimensional nuclear magnetic resonance spectroscopy and restrained molecular dynamics simulations. All proton signals were completely assigned, and interproton distances were determined using data from rotating-frame nuclear Overhauser enhancement. The backbone dihedral angles were deduced from measurements of coupling constants. The temperature dependence of the amide proton chemical shifts provided information about hydrogen bonding. Six probable solution conformations of viroisin were derived from the use of distance geometry and restrained molecular dynamics based on a set of distance constraints obtained from experimental data. The results of the structural analysis indicate that viroisin has a well ordered conformation in solution. In all these conformations the functional groups essential for toxicity orient themselves in the same direction so as to bind to the target proteins. This feature is consistent with previous results about the formation of a hydrophobic pocket on one side of the molecule.
使用二维核磁共振光谱和受限分子动力学模拟分析了毒伞肽（viroisin）的构象，毒伞肽是来自毒蝇伞（Amanita virosa）的病毒毒素家族的单环毒性七肽。所有质子信号都被完全归属，并且使用来自旋转框架核Overhauser增强的数据确定了质子间距离。从耦合常数的测量中推导出主链二面角。酰胺质子化学位移的温度依赖性提供了有关氢键的信息。基于从实验数据获得的一组距离约束，使用距离几何和受限分子动力学得出了毒伞肽的六种可能的溶液构象。结构分析结果表明，毒伞肽在溶液中具有良好的有序构象。在所有这些构象中，对毒性至关重要的官能团都朝着相同的方向排列，以便与靶蛋白结合。这一特征与先前关于分子一侧形成疏水口袋的结果一致。
