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

doi:10.1002/chem.201701591

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.

Type de document :

Article dans une revue

Chemistry - A European Journal, Wiley-VCH Verlag, 2017, 23 (37), pp.8800-8805 〈10.1002/chem.201701591 〉

Domaine :

Chimie / Chimie théorique et/ou physique

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https://hal-cea.archives-ouvertes.fr/cea-01571665
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Soumis le : jeudi 3 août 2017 - 11:48:15
Dernière modification le : jeudi 15 mars 2018 - 15:03:58

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

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