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The Coenzyme A Level Modulator Hopantenate (HoPan) Inhibits Phosphopantotenoylcysteine Synthetase Activity

ACS Chem Biol. 2021-09; 
Konrad J Mostert, Nandini Sharma, Marianne van der Zwaag, Roxine Staats, Lizbé Koekemoer, Ruchi Anand, Ody C M Sibon, Erick Strauss
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Custom Vector Construction … coli, synthesized, and provided in pUC vectors flanked by appropriate restriction enzyme cleavage sites by GenScript USA Inc. The sequence encoding hPANK1β (UniProt/Q8TE04.2) was subcloned into the pET20b expression vector using the NdeI and XhoI restriction sites, … Get A Quote

摘要

The pantothenate analogue hopantenate (HoPan) is widely used as a modulator of coenzyme A (CoA) levels in cell biology and disease models─especially for pantothenate kinase associated neurodegeneration (PKAN), a genetic disease rooted in impaired CoA metabolism. This use of HoPan was based on reports that it inhibits pantothenate kinase (PanK), the first enzyme of CoA biosynthesis. Using a combination of enzyme kinetic studies, crystal structure analysis, and experiments in a typical PKAN cell biology model, we demonstrate that instead of inhibiting PanK, HoPan relies on it for metabolic activation. Once phosphorylated, HoPan inhibits the next enzyme in the CoA pathway─phosphopantothenoylcysteine synthetas... More

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