Origin of Pressure Resistance in Deep-Sea Lactate Dehydrogenase.

High hydrostatic pressure has a dramatic effect on biochemical systems, as exposure to high pressure can result in structural perturbations ranging from dissociation of protein complexes to complete denaturation. The deep ocean presents an interesting paradox since it is teeming with life despite the high-pressure environment. This is due to evolutionary adaptations in deep-sea organisms, such as amino acid substitutions in their proteins, which aid in resisting the denaturing effects of pressure. However, the physicochemical mechanism by which these substitutions can induce pressure resistance remains unknown. Here, we use molecular dynamics simulations to study pressure-adapted lactate dehydrogenase from the deep-sea abyssal grenadier (