Chiancone E, Boffi A
CNR Center of Molecular Biology and Department of Biochemical Sciences, University La Sapienza, Rome, Italy.
Biophys Chem. 2000 Aug 30;86(2-3):173-8. doi: 10.1016/s0301-4622(00)00162-9.
The homodimeric cooperative hemoglobin from the mollusk Scapharca inaequivalvis displays an unusual subunit assembly with respect to vertebrate hemoglobins. The intersubunit contact region is formed by the two heme-carrying E and F helices, which bring the two hemes in contact with each other. At variance with tetrameric vertebrate hemoglobins, the ligand binding is not accompanied by a significant quaternary transition. The major ligand-linked changes are tertiary and are limited to the heme pocket and subunit interface. These unique structural features of HbI are not easily reconciled with the classical thermodynamic models used to describe cooperative ligand binding in vertebrate hemoglobins. The lack of distinct quaternary states and the absence of allosteric effectors suggested that cooperativity in HbI is entirely homotropic in origin. Thereafter, high resolution X-ray crystallographic data displayed the preferential binding of water molecules at the intersubunit interface in the unliganded protein with respect to the liganded one. These ordered water molecules were thus proposed to act as heterotropic effectors in HbI. The contribution of specific water binding to the observed cooperativity in HbI is discussed in the framework of the enthalpy-entropy compensation effect emerging from previous accurate equilibrium oxygen binding measurements.
来自不等蛤（Scapharca inaequivalvis）的同二聚体协同血红蛋白在亚基组装方面与脊椎动物血红蛋白不同寻常。亚基间的接触区域由携带血红素的E和F螺旋形成，这使得两个血红素相互接触。与四聚体脊椎动物血红蛋白不同，配体结合并不伴随着显著的四级结构转变。主要的配体连接变化是三级结构的，并且仅限于血红素口袋和亚基界面。血红蛋白I（HbI）的这些独特结构特征与用于描述脊椎动物血红蛋白中协同配体结合的经典热力学模型难以协调。缺乏明显的四级结构状态以及变构效应物的缺失表明，HbI中的协同性完全源于同促效应。此后，高分辨率X射线晶体学数据显示，相对于结合配体的蛋白质，未结合配体的蛋白质中亚基间界面处水分子优先结合。因此，这些有序水分子被认为在HbI中充当异促效应物。在先前精确的平衡氧结合测量所产生的焓 - 熵补偿效应的框架内，讨论了特定水分子结合对HbI中观察到的协同性的贡献。
