Bhattacharyya J, Bhattacharyya M, Chakrabarty A S, Chaudhuri U, Poddar R K
Department of Biophysics, Molecular Biology and Genetics, University of Calcutta, India.
Biochem Pharmacol. 1994 Jun 1;47(11):2049-53. doi: 10.1016/0006-2952(94)90080-9.
The mode and nature of the binding of chlorpromazine (CPZ), a psychotropic drug, with myoglobin, a monomeric muscle protein, were studied spectrofluorometrically and the results compared with those from the binding of CPZ to hemoglobin, a tetrameric allosteric protein from red blood cells (RBC). CPZ interacted with myoglobin in a non-cooperative mode, with a binding constant of 8.4 x 10(3) M-1 in 0.145 M NaCl, pH 6.8, whereas in the case of hemoglobin this interaction was found to be positively cooperative with a binding constant of 4.2 x 10(3) M-1. The interaction of CPZ with myoglobin was not influenced by the NaCl molarity of the solution, whereas CPZ interaction with hemoglobin significantly decreased with increasing NaCl molarity, indicating that CPZ-hemoglobin binding is mostly electrostatic in nature, whereas that of the CPZ-myoglobin complex is of a non-electrostatic type. Thermodynamic analysis revealed that binding of CPZ to hemoglobin was exothermic (delta H degrees = -2.65 kcal/mol), whereas binding to myoglobin was endothermic (delta H degrees = + 1.39 kcal/mol) with a high entropic contribution (delta S degrees = +23 cal/degree/mol), suggesting that CPZ binding to myoglobin is hydrophobic in nature. Such contrasting binding features of this drug have been discussed in the light of a typical subunit interaction property present and absent in hemoglobin and myoglobin, respectively.
采用荧光光谱法研究了精神药物氯丙嗪（CPZ）与单体肌肉蛋白肌红蛋白的结合模式和性质，并将结果与CPZ与血红蛋白（一种来自红细胞（RBC）的四聚体变构蛋白）的结合结果进行了比较。在0.145 M NaCl、pH 6.8条件下，CPZ以非协同模式与肌红蛋白相互作用，结合常数为8.4×10³ M⁻¹，而在血红蛋白的情况下，这种相互作用被发现是正协同的，结合常数为4.2×10³ M⁻¹。CPZ与肌红蛋白的相互作用不受溶液NaCl摩尔浓度的影响，而CPZ与血红蛋白的相互作用随着NaCl摩尔浓度的增加而显著降低，这表明CPZ与血红蛋白的结合主要是静电性质的，而CPZ与肌红蛋白复合物的结合是非静电类型的。热力学分析表明，CPZ与血红蛋白的结合是放热的（ΔH° = -2.65 kcal/mol），而与肌红蛋白的结合是吸热的（ΔH° = +1.39 kcal/mol），具有较高的熵贡献（ΔS° = +23 cal/°/mol），这表明CPZ与肌红蛋白的结合本质上是疏水的。根据血红蛋白和肌红蛋白中分别存在和不存在的典型亚基相互作用特性，讨论了这种药物的这种对比性结合特征。
