Abstract
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.
