Activity-Based Probes for the High Temperature Requirement A Serine Proteases.,ACS Chemical Biology

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Activity-Based Probes for the High Temperature Requirement A Serine Proteases.
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2020-08-04 , DOI: 10.1021/acschembio.0c00279
Ho Yeon Nam ₁ , Dasom Song ₁ , Jinny Eo ₂ , Na-Eun Choi ₂ , Jong-Ah Hong ₂ , Kyung Tae Hong ₃ , Jun-Seok Lee ₃ , Jiwon Seo ₁ , Jiyoun Lee ₂

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The high temperature requirement A (HTRA) family of serine proteases mediates protein quality control. These proteins process misfolded proteins in several diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD). While their structures and activation mechanisms have been studied, the precise details of the regulation of their activity under physiological conditions have not been completely elucidated, partly due to the lack of suitable chemical probes. In the present study, we developed novel activity-based probes (ABPs) targeting the HTRAs and demonstrated their utility in the monitoring and quantification of changes in enzyme activity in live cells. Using our probes, we found the activity of HTRA1 to be highly elevated in an AD-like cell-based model. We also observed the active HTRA2 in live cells by using a mitochondrion-targeted probe. We believe that our probes can serve as a useful tool to study the role of human HTRAs in neurodegenerative diseases.

中文翻译：

针对高温要求的基于活性的探针 A 丝氨酸蛋白酶。

丝氨酸蛋白酶的高温要求 A (HTRA) 家族介导蛋白质质量控制。这些蛋白质在多种疾病中处理错误折叠的蛋白质，包括阿尔茨海默病 (AD) 和帕金森病 (PD)。虽然它们的结构和激活机制已被研究，但其在生理条件下活性调节的精确细节尚未完全阐明，部分原因是缺乏合适的化学探针。在本研究中，我们开发了针对 HTRA 的新型活性探针 (ABP)，并证明了它们在监测和量化活细胞酶活性变化方面的实用性。使用我们的探针，我们发现 HTRA1 的活性在 AD 样细胞模型中高度升高。我们还通过使用线粒体靶向探针观察了活细胞中的活性 HTRA2。我们相信我们的探针可以作为研究人类 HTRA 在神经退行性疾病中的作用的有用工具。

更新日期：2020-09-20

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