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Analogs of the Dopamine Metabolite 5,6-Dihydroxyindole Bind Directly to and Activate the Nuclear Receptor Nurr1

ACS PUBLICATIONS. 2021-06; 
Svetlana A. Kholodar, Geoffrey Lang, Wilian A. Cortopassi, Yoshie Iizuka, Harman S. Brah, Matthew P. Jacobson, and Pamela M. England
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Gene Synthesis The plasmid used for the expression of LAP2-tagged Nurr1 LBDs (LAP2 Nurr1) was prepared by GenScript (Piscataway, NJ) as the product of gene synthesis and subcloning into pET-21a(+) Vector (GenScript) using the Ndel and Xhol sites within the MCS. The protein sequence of the resulting protein is shown in Supporting Table 1. Mutants of LAP2 Nurr1 were prepared by GenScript starting from LAP2 Nurr1 vector. Get A Quote

摘要

The nuclear receptor-related 1 protein, Nurr1, is a transcription factor critical for the development and maintenance of dopamine-producing neurons in the substantia nigra pars compacta, a cell population that progressively loses the ability to make dopamine and degenerates in Parkinson’s disease. Recently, we demonstrated that Nurr1 binds directly to and is regulated by the endogenous dopamine metabolite 5,6-dihydroxyindole (DHI). Unfortunately, DHI is an unstable compound, and thus a poor tool for studying Nurr1 function. Here, we report that 5-chloroindole, an unreactive analog of DHI, binds directly to the Nurr1 ligand binding domain with micromolar affinity and stimulates the activity of Nurr1, including... More

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