TY - JOUR
TI - A New Potent Inhibitor of Glycogen Phosphorylase Reveals the Basicity of the Catalytic Site
AU - Michael Mamais
AU - Alessandra Degli0.25emEsposti
AU - Virginia Kouloumoundra
AU - Thomas Gustavsson
AU - Filippo Monti
AU - Alessandro Venturini
AU - Evangelia D. Chrysina
AU - Dimitra Markovitsi
AU - Thanasis Gimisis
JO - CHEMISTRY: A EUROPEAN JOURNAL
PY - 2017
VL - 23
TODO - 37
SP - 8800--8805
PB - Wiley
SN - 0947-6539
TODO - 10.1002/chem.201701591
TODO - X-ray crystallography,acridone based inhibitors,glycogen phosphorylase,optical spectra,quantum chemistry
TODO - 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 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 cal culations, 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.
ER -