Whisstock James C, Bottomley Stephen P
Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, Clayton Campus, Melbourne 3800, Australia.
Curr Opin Struct Biol. 2006 Dec;16(6):761-8. doi: 10.1016/j.sbi.2006.10.005. Epub 2006 Oct 31.
The native state of serpins represents a long-lived intermediate or metastable structure on the serpin folding pathway. Upon interaction with a protease, the serpin trap is sprung and the molecule continues to fold into a more stable conformation. However, thermodynamic stability can also be achieved through alternative, unproductive folding pathways that result in the formation of inactive conformations. Our increasing understanding of the mechanism of protease inhibition and the dynamics of native serpin structures has begun to reveal how evolution has harnessed the actual process of protein folding (rather than the final folded outcome) to elegantly achieve function. The cost of using metastability for function, however, is an increased propensity for misfolding.
丝氨酸蛋白酶抑制剂（serpin）的天然状态代表了其折叠途径上的一种长寿命中间体或亚稳态结构。与蛋白酶相互作用时，serpin陷阱被触发，分子继续折叠成更稳定的构象。然而，热力学稳定性也可以通过导致形成无活性构象的替代的、非生产性折叠途径来实现。我们对蛋白酶抑制机制和天然serpin结构动力学的日益深入的理解，已开始揭示进化是如何利用蛋白质折叠的实际过程（而非最终的折叠结果）来巧妙地实现功能的。然而，利用亚稳态实现功能的代价是错误折叠的倾向增加。
