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

doi:10.1016/j.febslet.2015.05.013

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

Research output: Contribution to journal › Article › Research › peer-review

37 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 K_is of 13.4 and 7.5 μM, in contrast to gallic acid which displays K_is 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 language	English
Article number	37169
Pages (from-to)	1787-1794
Number of pages	8
Journal	FEBS Letters
Volume	589
Issue number	15
DOIs	https://doi.org/10.1016/j.febslet.2015.05.013
Publication status	Published - 8 Jul 2015
Externally published	Yes

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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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.",

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author = "Efthimios Kyriakis and Stravodimos, {George A.} and Kantsadi, {Anastassia L.} and Chatzileontiadou, {Demetra S M} and Skamnaki, {Vassiliki T.} and Leonidas, {Demetres D.}",

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AU - Kyriakis, Efthimios

AU - Stravodimos, George A.

AU - Kantsadi, Anastassia L.

AU - Chatzileontiadou, Demetra S M

AU - Skamnaki, Vassiliki T.

AU - Leonidas, Demetres D.

PY - 2015/7/8

Y1 - 2015/7/8

N2 - 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.

AB - 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.

KW - Abbreviations GP glycogen phosphorylase

KW - Glc-1-P α-d-glucose 1-phosphate

KW - GPb rabbit muscle glycogen phosphorylase b

KW - PLP pyridoxal 5′-phosphate

KW - r.m.s.d. root-mean-square displacement

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DO - 10.1016/j.febslet.2015.05.013

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AN - SCOPUS:84934442977

SN - 0014-5793

VL - 589

SP - 1787

EP - 1794

JO - FEBS Letters

JF - FEBS Letters

IS - 15

M1 - 37169

ER -

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

Abstract

Keywords

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