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ID: ALA4622837

Journal: Bioorg Med Chem Lett

Title: Finding the mechanism of esterase D activation by a small molecule.

Authors: Chen X, Yang Y, Su L, Cui X, Shao J, Liu S, Zhao B, Miao J.

Abstract: 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.

CiteXplore: 32247735

DOI: 10.1016/j.bmcl.2020.127150