Finding the mechanism of esterase D activation by a small molecule

被引：11

作者：

Chen, Xinpeng ^{[1
,2
]}

Yang, Yuejun ^{[1
]}

Su, Le ^{[1
]}

Cui, Xiaoling ^{[1
]}

Shao, Jing ^{[1
]}

Liu, Shuyan ^{[1
]}

Zhao, Baoxiang ^{[3
]}

Miao, Junying ^{[1
,4
,5
]}

机构：

[1] Shandong Univ, Sch Life Sci, Shandong Prov Key Lab Anim Cells & Dev Biol, Qingdao 266237, Peoples R China

[2] Hubei Normal Univ, Natl Demonstrat Ctr Expt Biol Educ, Sch Life Sci, Hubei Key Lab Edible Wild Plants Conservat & Util, Huangshi 435002, Hubei, Peoples R China

[3] Shandong Univ, Sch Chem & Chem Engn, Inst Organ Chem, Jinan 250100, Peoples R China

[4] Shandong Univ, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Minist Educ, Qilu Hosp, Jinan 250012, Peoples R China

[5] Shandong Univ, Chinese Minist Hlth, Qilu Hosp, Jinan 250012, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2020年 / 30卷 / 11期

基金：

中国国家自然科学基金;

关键词：

ESD activation; FPD5; Mono-ubiquitination; CANCER;

D O I：

10.1016/j.bmcl.2020.127150

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

People with reduced esterase D (ESD) activity are susceptible to many diseases. However, how to activate ESD is still unknown. To address the question, we identified that 4-chloro-2-(5-phenyl-1-(pyridin-2-yl)-4, 5-dihydro-1H-pyrazol-3-yl) phenol (FPD5) could be a good candidate activator for ESD activity. We found that FPD5 could increase ESD activity in a dose-dependent way. FPD5 bound directly to ESD at Lys180 rather than its ubiquitination site Lys213. Site-directed mutagenesis at the binding site or the ubiquitination site inhibited FPD5 action. FPD5 increased the level of ESD mono-ubiquitination and mutESD K213A completely inhibited this action. Our findings highlighted the activation mechanism of ESD via promoting the mono-ubiquitination of ESD.

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页数：5

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