Antioxid Redox Signal. 2013 May 1;18(13):1594-6. doi: 10.1089/ars.2012.5156. Epub 2013 Feb 25.
The major function of disulfide bonds is not only the stabilization of protein structures. Over the last 30 years, a change in perspective took place driven by groundbreaking experiments, which promoted disulfide bonds to central players in essential thiol-disulfide exchange reactions involved in signal transduction, thiol protection, and redox homeostasis regulation. This new view stimulated redox research and led to the discovery of novel redox pathways, redox enzymes, and new low-molecular-weight thiols. These redox-sensitive molecules operate along diverse pathways via a dynamic thiol-disulfide mechanism in which disulfide bonds are reversibly formed and reduced, thereby switching the molecules between different conformational and functional states. It is now clear that disulfide bonds play a pivotal role in cellular reduction and oxidation processes. However, in spite of the fundamental cell biological and medical importance of the thiol-disulfide exchange switches, we are only beginning to understand their principles of specificity, their mechanism of action, and their role in signal transduction. Our further progress in understanding the thiol-disulfide switches will strongly depend on the chemical tools and on the technological advances that will be made in the development of new methodologies.
二硫键的主要功能不仅在于稳定蛋白质结构。在过去的 30 年中，由于具有开创性的实验，人们的观点发生了变化，这些实验促使二硫键成为信号转导、巯基保护和氧化还原稳态调节中所涉及的基本巯基-二硫键交换反应的核心参与者。这种新观点激发了氧化还原研究，并导致了新的氧化还原途径、氧化还原酶和新的低分子量巯基的发现。这些氧化还原敏感的分子通过动态的巯基-二硫键机制在不同的途径中运作，其中二硫键可以可逆地形成和还原，从而使分子在不同的构象和功能状态之间切换。现在很明显，二硫键在细胞的还原和氧化过程中起着关键作用。然而，尽管巯基-二硫键交换开关具有基本的细胞生物学和医学重要性，但我们才刚刚开始了解它们的特异性原则、作用机制以及它们在信号转导中的作用。我们在理解巯基-二硫键开关方面的进一步进展将强烈依赖于化学工具和新技术的发展，这些将为新方法的开发提供支持。
