Natural flavonoids as antidiabetic agents. The binding of gallic and ellagic acids to glycogen phosphorylase b

Efthimios Kyriakis, George A. Stravodimos, Anastassia L. Kantsadi, Demetra S M Chatzileontiadou, Vassiliki T. Skamnaki, Demetres D. Leonidas

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23 Citations (Scopus)

Abstract

Abstract We present a study on the binding of gallic acid and its dimer ellagic acid to glycogen phosphorylase (GP). Ellagic acid is a potent inhibitor with Kis of 13.4 and 7.5 μM, in contrast to gallic acid which displays Kis of 1.7 and 3.9 mM for GPb and GPa, respectively. Both compounds are competitive inhibitors with respect to the substrate, glucose-1-phoshate, and non-competitive to the allosteric activator, AMP. However, only ellagic acid functions with glucose in a strongly synergistic mode. The crystal structures of the GPb-gallic acid and GPb-ellagic acid complexes were determined at high resolution, revealing that both ligands bind to the inhibitor binding site of the enzyme and highlight the structural basis for the significant difference in their inhibitory potency.

Original languageEnglish
Article number37169
Pages (from-to)1787-1794
Number of pages8
JournalFEBS Letters
Volume589
Issue number15
DOIs
Publication statusPublished - 8 Jul 2015
Externally publishedYes

Keywords

  • Abbreviations GP glycogen phosphorylase
  • Glc-1-P α-d-glucose 1-phosphate
  • GPb rabbit muscle glycogen phosphorylase b
  • PLP pyridoxal 5′-phosphate
  • r.m.s.d. root-mean-square displacement

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