A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.
Chemical Faculty, Lomonosov Moscow State University, Moscow, Russia.
Biochim Biophys Acta Gen Subj. 2020 Sep;1864(9):129636. doi: 10.1016/j.bbagen.2020.129636. Epub 2020 May 17.
Proline specific peptidases (PSPs) are a unique group of enzymes that specifically cleave bonds formed by a proline residue. The study of PSPs is important due to their role in the maturation and degradation of peptide hormones and neuropeptides. In addition, changes in the activity of PSPs can result in pathological conditions, including various types of cancer.
PSPs annotated from the Homo sapiens genome were compared and classified by their physicochemical and biochemical features and roles in vital processes. In addition to catalytic activity, we discuss non-enzymatic functions that may regulate cellular activity.
PSPs apparently have multiple functions in animals. Two functions rely on the catalytic activity of the enzyme: one involved in a regulatory pathway associated with the ability of many PSPs to hydrolyze peptide hormones and neuropeptides, and the other involved in the trophic pathway associated with the proteolysis of total cellular protein or Pro-containing dietary proteins in the digestive tract. PSPs also participate in signal transduction without proteolytic activity by forming protein-protein interactions that trigger or facilitate the performance of certain functions.
PSPs are underestimated as a unique component of the normal human peptidase degradome, providing the body with free proline. A comparative analysis of PSPs can guide research to develop inhibitors that counteract the abnormalities associated with changes in PSP activity, and identify natural substrates of PSPs that will enable better understanding of the mechanisms of the action of PSPs in biological processes and disease.
脯氨酸特异性肽酶（PSPs）是一组独特的酶，专门切割由脯氨酸残基形成的键。研究 PSPs 很重要，因为它们在肽激素和神经肽的成熟和降解中起作用。此外，PSPs 活性的变化可能导致病理状况，包括各种类型的癌症。
比较了从人类基因组注释的 PSPs，并根据其理化性质和在重要过程中的生化作用进行分类。除了催化活性外，我们还讨论了可能调节细胞活性的非酶功能。
PSPs 在动物中显然具有多种功能。两种功能依赖于酶的催化活性：一种与许多 PSP 水解肽激素和神经肽的能力相关的调节途径有关，另一种与营养途径有关，该途径与总细胞蛋白或消化道中含 Pro 的膳食蛋白的蛋白水解有关。PSPs 还通过形成触发或促进某些功能执行的蛋白质-蛋白质相互作用参与信号转导，而无需酶活性。
PSPs 作为正常人类肽酶降解组的一个独特组成部分被低估了，为机体提供了游离脯氨酸。对 PSPs 的比较分析可以指导研究开发抑制剂来对抗与 PSP 活性变化相关的异常，并鉴定 PSPs 的天然底物，这将有助于更好地理解 PSPs 在生物过程和疾病中的作用机制。
