Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10628-33. doi: 10.1073/pnas.1302284110. Epub 2013 Jun 10.
Entropic stabilization of native protein structures typically relies on strategies that serve to decrease the entropy of the unfolded state. Here we report, using a combination of experimental and computational approaches, on enhanced thermodynamic stability conferred by an increase in the configurational entropy of the folded state. The enhanced stability is observed upon modifications of a loop region in the enzyme acylphosphatase and is achieved despite significant enthalpy losses. The modifications that lead to increased stability, as well as those that result in destabilization, however, strongly compromise enzymatic activity, rationalizing the preservation of the native loop structure even though it does not provide the protein with maximal stability or kinetic foldability.
天然蛋白质结构的熵稳定性通常依赖于降低未折叠状态熵的策略。在这里，我们使用实验和计算相结合的方法报告了通过增加折叠状态的构象熵来赋予增强的热力学稳定性。在酰基磷酸酶的环区修饰后观察到增强的稳定性，尽管存在显著的焓损失。导致稳定性增加的修饰以及导致失稳的修饰，然而，强烈损害酶活性，证明即使天然环结构不能为蛋白质提供最大的稳定性或动力学折叠性，也需要保留它。
