Inhibition of protein phosphatase-1 and -2A by ellagitannins: structure-inhibitory potency relationships and influences on cellular systems

Zoltán Kónya, Bálint Bécsi, Andrea Kiss, Dániel Horváth, Mária Raics, Katalin E. Kövér, Beáta Lontay, Ferenc Erdődi

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Several ellagitannins inhibited the activity of protein phosphatase-1 (PP1) and -2 A (PP2A) catalytic subunits (PP1c and PP2Ac) with preferential suppression of PP1c over PP2Ac. The inhibitory potency for PP1c followed the order of tellimagrandin I > mahtabin A > praecoxin B > 1.2-Di-O-galloyl-4.6-(S)-HHDP-β-D-glucopyranose > pedunculagin with IC 50 values ranging from 0.20 µM to 2.47 µM. The interaction of PP1c and tellimagrandin I was assessed by NMR saturation transfer difference, surface plasmon resonance, isothermal titration calorimetry, and microscale thermophoresis based binding techniques. Tellimagrandin I suppressed viability and phosphatase activity of HeLa cells, while mahtabin A was without effect. Conversely, mahtabin A increased the phosphorylation level of SNAP-25 Thr138 and suppressed exocytosis of cortical synaptosomes, whereas tellimagrandin I was without influence. Our results establish ellagitannins as partially selective inhibitors of PP1 and indicate that these polyphenols may act distinctly in cellular systems depending on their membrane permeability and/or their actions on cell membranes.

Original languageEnglish
Pages (from-to)500-509
Number of pages10
JournalJournal of enzyme inhibition and medicinal chemistry
Issue number1
Publication statusPublished - Jan 1 2019



  • Tellimagrandin I
  • mahtabin A
  • protein phosphatase-1
  • protein phosphatase-2A
  • synaptosomal exocytosis

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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