| Autor: |
Maguire SH; Department of Chemistry, Vancouver Island University, Nanaimo V9R 5S5, Canada., Mercer SR; Department of Chemistry, Vancouver Island University, Nanaimo V9R 5S5, Canada., Wiebe HA; Department of Chemistry, Vancouver Island University, Nanaimo V9R 5S5, Canada.; Department of Chemistry, University of Victoria, Victoria V8P 5C2, Canada.; Department of Chemistry, University of the Fraser Valley, Abbotsford V2S 7M7, Canada. |
| Abstrakt: |
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 ( Coryphaenoides armatus ), in comparison with that of the shallow-water Atlantic cod ( Gadus morhua ). We examined structural, thermodynamic and volumetric contributions to pressure resistance, and report that the amino acid substitutions result in a decrease in volume of the deep-sea protein accompanied by a decrease in thermodynamic stability of the native protein. Our simulations at high pressure also suggest that differences in compressibility may be important for understanding pressure resistance in deep-sea proteins. |
