Gurung Deepti, Danielson Jacob A, Tasnim Afsara, Zhang Jian-Ting, Zou Yue, Liu Jing-Yuan
Department of Medicine, University of Toledo College of Medicine, Toledo, OH 43614, USA.
Department of Cell and Cancer Biology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
Biology (Basel). 2023 Jul 14;12(7):1008. doi: 10.3390/biology12071008.
Proline isomerization, the process of interconversion between the - and -forms of proline, is an important and unique post-translational modification that can affect protein folding and conformations, and ultimately regulate protein functions and biological pathways. Although impactful, the importance and prevalence of proline isomerization as a regulation mechanism in biological systems have not been fully understood or recognized. Aiming to fill gaps and bring new awareness, we attempt to provide a wholistic review on proline isomerization that firstly covers what proline isomerization is and the basic chemistry behind it. In this section, we vividly show that the cause of the unique ability of proline to adopt both - and -conformations in significant abundance is rooted from the steric hindrance of these two forms being similar, which is different from that in linear residues. We then discuss how proline isomerization was discovered historically followed by an introduction to all three types of proline isomerases and how proline isomerization plays a role in various cellular responses, such as cell cycle regulation, DNA damage repair, T-cell activation, and ion channel gating. We then explore various human diseases that have been linked to the dysregulation of proline isomerization. Finally, we wrap up with the current stage of various inhibitors developed to target proline isomerases as a strategy for therapeutic development.
脯氨酸异构化是脯氨酸α-型和β-型之间相互转换的过程，是一种重要且独特的翻译后修饰，它可以影响蛋白质折叠和构象，最终调节蛋白质功能和生物途径。尽管脯氨酸异构化具有重要影响，但作为生物系统中的一种调节机制，其重要性和普遍性尚未得到充分理解或认识。为了填补空白并带来新的认识，我们试图对脯氨酸异构化进行全面综述，首先介绍脯氨酸异构化是什么以及其背后的基本化学原理。在这一部分，我们清晰地表明，脯氨酸能够大量采用α-型和β-构象这一独特能力的原因，源于这两种构象的空间位阻相似，这与线性残基不同。接着，我们讨论脯氨酸异构化在历史上是如何被发现的，随后介绍所有三种类型的脯氨酸异构酶，以及脯氨酸异构化在各种细胞反应中如何发挥作用，如细胞周期调控、DNA损伤修复、T细胞活化和离子通道门控。然后，我们探讨了与脯氨酸异构化失调相关的各种人类疾病。最后，我们总结了目前作为治疗开发策略而研发的针对脯氨酸异构酶的各种抑制剂的情况。
