Knott R, Hansen S, Henderson S
ANP Program, Australian Nuclear Science and Technology Organisation, Menai NSW.
J Struct Biol. 1994 May-Jun;112(3):192-8. doi: 10.1006/jsbi.1994.1020.
Small angle X-ray scattering (SAXS) was applied to the binding of the immunosuppressant drug cyclosporin-A to the protein calmodulin. Guinier analysis of the SAXS profiles yielded a radius of gyration, Rg, of 19.7 +/- 0.3 A for the native protein and 16.9 +/- 0.3 A for the drug/protein complex. Maximum entropy (maxent) methods of data analysis were used to calculate the distance distribution function, p(r). From this analysis, the Rg for the native protein is 20.9 +/- 0.1 A and that for the complex 16.7 +/- 0.1 A. The measured SAXS profiles and the derived p(r) for calmodulin agree with profiles calculated from the crystallographic structure of calmodulin. Major structural changes are induced in calmodulin on binding cyclosporin-A. A model consistent with the observed scattering profiles is an ellipsoid with major axes 55 and 36 A. Molecular modeling of the calmodulin molecule suggests that bond rotation in the flexible alpha-helix linker region produces models consistent with the above observations.
小角X射线散射（SAXS）被应用于免疫抑制剂环孢菌素A与钙调蛋白的结合研究。对SAXS图谱进行吉尼尔分析得出，天然蛋白的回转半径Rg为19.7±0.3 Å，药物/蛋白复合物的回转半径Rg为16.9±0.3 Å。采用最大熵（maxent）数据分析方法计算距离分布函数p(r)。通过该分析，天然蛋白的Rg为20.9±0.1 Å，复合物的Rg为16.7±0.1 Å。测得的钙调蛋白SAXS图谱及推导的p(r)与根据钙调蛋白晶体结构计算出的图谱相符。环孢菌素A与钙调蛋白结合时会引起钙调蛋白的主要结构变化。与观察到的散射图谱相符的模型是一个长轴为55 Å和36 Å的椭球体。钙调蛋白分子的分子模拟表明，柔性α-螺旋连接区的键旋转产生了与上述观察结果相符的模型。
