Epigallocatechin-3-gallate and penta-O-galloyl-β-d-glucose inhibit protein phosphatase-1

A. Kiss, Bálint Bécsi, Bernadett Kolozsvári, I. Komáromi, K. Kövér, F. Erdődi

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Protein phosphatase-1 (PP1) and protein phosphatase-2A (PP2A) are responsible for the dephosphorylation of the majority of phosphoserine/threonine residues in cells. In this study, we show that (-)-epigallocatechin-3-gallate (EGCG) and 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG), polyphenolic constituents of green tea and tannins, inhibit the activity of the PP1 recombinant δ-isoform of the PP1 catalytic subunit and the native PP1 catalytic subunit (PP1c) with IC50 values of 0.47-1.35 μm and 0.26-0.4 μm, respectively. EGCG and PGG inhibit PP2Ac less potently, with IC50 values of 15 and 6.6 μm, respectively. The structure-inhibitory potency relationships of catechin derivatives suggests that the galloyl group may play a major role in phosphatase inhibition. The interaction of EGCG and PGG with PP1c was characterized by NMR and surface plasmon resonance-based binding techniques. Competitive binding assays and molecular modeling suggest that EGCG docks at the hydrophobic groove close to the catalytic center of PP1c, partially overlapping with the binding surface of microcystin-LR or okadaic acid. This hydrophobic interaction is further stabilized by hydrogen bonding via hydroxyl/oxo groups of EGCG to PP1c residues. Comparative docking shows that EGCG binds to PP2Ac in a similar manner, but in a distinct pose. Long-term treatment (24 h) with these compounds and other catechins suppresses the viability of HeLa cells with a relative effectiveness reminiscent of their in vitro PP1c-inhibitory potencies. The above data imply that the phosphatase-inhibitory features of these polyphenols may be implicated in the wide spectrum of their physiological influence.

Original languageEnglish
Pages (from-to)612-626
Number of pages15
JournalFEBS Journal
Volume280
Issue number2
DOIs
Publication statusPublished - Jan 2013

Fingerprint

Protein Phosphatase 1
Rubiaceae
Catalytic Domain
Glucose
Catechin
Phosphoric Monoester Hydrolases
Inhibitory Concentration 50
Phosphoserine
Protein Phosphatase 2
Okadaic Acid
Docks
Molecular modeling
Competitive Binding
Surface Plasmon Resonance
Tannins
Surface plasmon resonance
Polyphenols
Tea
Threonine
Hydrogen Bonding

Keywords

  • green tea and tannin polyphenols
  • molecular modeling
  • NMR saturation transfer difference
  • Ser/Thr-specific protein phosphatase-1 and protein phosphatase-2A
  • surface plasmon resonance

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Epigallocatechin-3-gallate and penta-O-galloyl-β-d-glucose inhibit protein phosphatase-1. / Kiss, A.; Bécsi, Bálint; Kolozsvári, Bernadett; Komáromi, I.; Kövér, K.; Erdődi, F.

In: FEBS Journal, Vol. 280, No. 2, 01.2013, p. 612-626.

Research output: Contribution to journalArticle

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