The mesophilic inorganic pyrophosphatase from Escherichia coli (EcPPase) retains function at 353 K, the physiological temperature of hyperthermophilic Thermococcus thioreducens, whereas the homolog protein (TtPPase) from this hyperthermophilic organism cannot function at room temperature. To explain this asymmetric behavior, we examined structural and dynamical properties of the two proteins using molecular dynamics simulations. The global flexibility of TtPPase is significantly higher than its mesophilic homolog at all tested temperature/pressure conditions. However, at 353 K, EcPPase reduces its solvent-exposed surface area and increases subunit compaction while maintaining flexibility in its catalytic pocket. In contrast, TtPPase lacks this adaptability and has increased rigidity and reduced protein/water interactions in its catalytic pocket at room temperature, providing a plausible explanation for its inactivity near room temperature.

中文翻译：

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高温下嗜温焦磷酸酶功能：分子动力学模拟研究

来自大肠杆菌的嗜温无机焦磷酸酶 (EcPPase) 在 353 K（超嗜热硫还原热球菌的生理温度）下保持功能，而来自这种超嗜热生物的同源蛋白 (TtPPase) 在室温下无法发挥作用。为了解释这种不对称行为，我们使用分子动力学模拟检查了两种蛋白质的结构和动力学特性。在所有测试的温度/压力条件下，TtPPase 的全局灵活性明显高于其嗜温同系物。然而，在 353 K 时，EcPPase 减少了其暴露于溶剂的表面积并增加了亚基压实，同时保持其催化口袋的灵活性。相比之下，