Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
College of Pharmaceutical Sciences, Ritsumeikan University, Nojihigashi 1-1-1, Kusatsu 525-8577, Japan.
Biochim Biophys Acta Proteins Proteom. 2019 Mar;1867(3):350-358. doi: 10.1016/j.bbapap.2018.10.014. Epub 2018 Oct 24.
Hydrostatic pressure alters the free energy of proteins by a few kJ mol, with the amount depending on their partial molar volumes. Because the folded ground state of a protein contains cavities, it is always a state of large partial molar volume. Therefore pressure always destabilises the ground state and increases the population of partially and completely unfolded states. This is a mild and reversible conformational change, which allows the study of excited states under thermodynamic equilibrium conditions. Many of the excited states studied in this way are functionally relevant; they also seem to be very similar to kinetic folding intermediates, thus suggesting that evolution has made use of the 'natural' dynamic energy landscape of the protein fold and sculpted it to optimise function. This includes features such as ligand binding, structural change during the catalytic cycle, and dynamic allostery.
静水压通过改变蛋白质的自由能几 kJ/mol，这一数值取决于它们的偏摩尔体积。由于蛋白质的折叠基态包含空穴，因此它总是具有较大的偏摩尔体积。因此，压力总是使基态不稳定，并增加部分和完全展开状态的丰度。这是一种温和且可逆的构象变化，可在热力学平衡条件下研究激发态。以这种方式研究的许多激发态与功能相关；它们似乎也与动力学折叠中间体非常相似，这表明进化利用了蛋白质折叠的“自然”动态能量景观，并对其进行了优化以实现功能。这包括配体结合、催化循环中的结构变化以及动态变构等特征。
