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

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 〉
Liste complète des métadonnées

https://hal-cea.archives-ouvertes.fr/cea-01571665
Contributeur : Caroline Lebe <>
Soumis le : jeudi 3 août 2017 - 11:48:15
Dernière modification le : jeudi 11 janvier 2018 - 06:27:30

Identifiants

Citation

Michael Mamais, Alessandra Degli esposti, Virginia Kouloumoundra, Thomas Gustavsson, Filippo Monti, et al.. A New Potent Inhibitor of Glycogen Phosphorylase Reveals the Basicity of the Catalytic Site . Chemistry - A European Journal, Wiley-VCH Verlag, 2017, 23 (37), pp.8800-8805 〈10.1002/chem.201701591 〉. 〈cea-01571665〉

Partager

Métriques

Consultations de la notice

111