Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, LRB 826, 364 Plantation Street, Worcester, MA, 01605, USA.
Program in Chemical Biology, University of Massachusetts Medical School, LRB 826, 364 Plantation Street, Worcester, MA, 01605, USA.
Curr Top Microbiol Immunol. 2019;420:233-251. doi: 10.1007/82_2018_132.
Protein arginine deiminases (PADs) catalyze the post-translational deimination of peptidyl arginine to form peptidyl citrulline. This modification is increased in multiple inflammatory diseases and in certain cancers. PADs regulate a variety of signaling pathways including apoptosis, terminal differentiation, and transcriptional regulation. Activity-based protein profiling (ABPP) probes have been developed to understand the role of the PADs in vivo and to investigate the effect of protein citrullination in various pathological conditions. Furthermore, these ABPPs have been utilized as a platform for high-throughput inhibitor discovery. This review will showcase the development of ABPPs targeting the PADs. In addition, it provides a brief overview of PAD structure and function along with recent advances in PAD inhibitor development.
蛋白质精氨酸脱亚氨酶（PADs）催化肽基精氨酸的翻译后脱亚氨基作用，形成肽基瓜氨酸。这种修饰在多种炎症性疾病和某些癌症中增加。PADs 调节多种信号通路，包括细胞凋亡、终末分化和转录调控。活性依赖的蛋白质谱（ABPP）探针已被开发出来，以了解 PADs 在体内的作用，并研究蛋白质瓜氨酸化在各种病理条件下的影响。此外，这些 ABPPs 已被用作高通量抑制剂发现的平台。这篇综述将展示针对 PADs 的 ABPP 的发展。此外，它还简要概述了 PAD 的结构和功能以及 PAD 抑制剂开发的最新进展。
