Stabilization of thermophilic enzymes by pressure

Many thermophilic enzymes exhibit increased thermal stability at high pressures. Improved stability under pressure appears to be closely related to enzyme thermostability; however, the underlying mechanism(s) of this relationship is not yet clear. We are investigating structure-function relationships associated with the pressure-stabilization of enzymes, particularly thermophilic enzymes from pressure-adapted sources (e.g., glutamate dehydrogenase (GDH) from the deep-sea hyperthermophile Pyrococcus endeavori). Surprisingly, recombinant GDH from Pyrococcus furiosus is stabilized ca. 800-fold at 103 degrees C by 500 atm pressure, whereas the closely related wild-type enzyme from P. endeavori is unaffected by pressure. This behavior suggests that useful insights into enzyme structure-stability relationships can be obtained by comparing the structures of the two proteins, and that subtle structural differences can have a major impact on thermostability and pressure stabilization.