A New Potent Inhibitor of Glycogen Phosphorylase Reveals the Basicity of the Catalytic Site

Michael Mamais; Alessandra Degli esposti; Virginia Kouloumoundra; Thomas Gustavsson; Filippo Monti; Alessandro Venturini; Evangelia D. Chrysina; Dimitra Markovitsi; Thanasis Gimisis

A New Potent Inhibitor of Glycogen Phosphorylase Reveals the Basicity of the Catalytic Site

Michael Mamais ¹ Alessandra Degli esposti ² Virginia Kouloumoundra ¹ Thomas Gustavsson ^{3, 4} Filippo Monti ⁵ Alessandro Venturini ² Evangelia D. Chrysina ⁶ Dimitra Markovitsi ^{3, 4} Thanasis Gimisis ¹

1 National and Kapodistrian University of Athens

2 ISOF-CNR - Istituto per la Sintesi Organica e la Fotoreattività

3 LIDyl - Laboratoire Interactions, Dynamique et Lasers (ex SPAM)

4 DICO - Biomolécules Excitées

IRAMIS - Institut Rayonnement Matière de Saclay, LIDyl - Laboratoire Interactions, Dynamique et Lasers (ex SPAM)

5 Gulliver

6 National Hellenic Research Foundation [Athens]

Abstract : The design and synthesis of a glucose-based acridone derivative (GLAC), a potent inhibitor of glycogen phosphorylase (GP) are described. GLAC is the first inhibitor of glycogen phosphorylase, the electronic absorption properties of which are clearly distinguishable from those of the enzyme. This allows probing subtle interactions in the catalytic site. The GLAC absorption spectra, associated with X-ray crystallography and quantum chemistry calculations, reveal that part of the catalytic site of GP behaves as a highly basic environment in which GLAC exists as a bis-anion. This is explained by water-bridged hydrogen-bonding interactions with specific catalytic site residues.

Document type :

Journal articles

Domain :

Chemical Sciences / Theoretical and/or physical chemistry

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https://hal-cea.archives-ouvertes.fr/cea-01571665
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Submitted on : Thursday, August 3, 2017 - 11:48:15 AM
Last modification on : Thursday, February 7, 2019 - 5:15:54 PM

A New Potent Inhibitor of Glycogen Phosphorylase Reveals the Basicity of the Catalytic Site

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A New Potent Inhibitor of Glycogen Phosphorylase Reveals the Basicity of the Catalytic Site

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