@article {36595,
	title = {The binding of beta- and gamma-cyclodextrins to glycogen phosphorylase b: kinetic and crystallographic studies},
	journal = {Protein SciProtein Sci},
	volume = {12},
	number = {9},
	year = {2003},
	note = {Pinotsis, NikosLeonidas, Demetres DChrysina, Evangelia DOikonomakos, Nikos GMavridis, Irene MengResearch Support, Non-U.S. Gov{\textquoteright}tProtein Sci. 2003 Sep;12(9):1914-24. doi: 10.1110/ps.03149503.},
	month = {Sep},
	pages = {1914-24},
	edition = {2003/08/22},
	abstract = {A number of regulatory binding sites of glycogen phosphorylase (GP), such as the catalytic, the inhibitor, and the new allosteric sites are currently under investigation as targets for inhibition of hepatic glycogenolysis under high glucose concentrations; in some cases specific inhibitors are under evaluation in human clinical trials for therapeutic intervention in type 2 diabetes. In an attempt to investigate whether the storage site can be exploited as target for modulating hepatic glucose production, alpha-, beta-, and gamma-cyclodextrins were identified as moderate mixed-type competitive inhibitors of GPb (with respect to glycogen) with K(i) values of 47.1, 14.1, and 7.4 mM, respectively. To elucidate the structural basis of inhibition, we determined the structure of GPb complexed with beta- and gamma-cyclodextrins at 1.94 A and 2.3 A resolution, respectively. The structures of the two complexes reveal that the inhibitors can be accommodated in the glycogen storage site of T-state GPb with very little change of the tertiary structure and provide a basis for understanding their potency and subsite specificity. Structural comparisons of the two complexes with GPb in complex with either maltopentaose (G5) or maltoheptaose (G7) show that beta- and gamma-cyclodextrins bind in a mode analogous to the G5 and G7 binding with only some differences imposed by their cyclic conformations. It appears that the binding energy for stabilization of enzyme complexes derives from hydrogen bonding and van der Waals contacts to protein residues. The binding of alpha-cyclodextrin and octakis (2,3,6-tri-O-methyl)-gamma-cyclodextrin was also investigated, but none of them was bound in the crystal; moreover, the latter did not inhibit the phosphorylase reaction.},
	keywords = {*alpha-Cyclodextrins, *beta-Cyclodextrins, *gamma-Cyclodextrins, Animals, Binding Sites, circular dichroism, Crystallography, X-Ray, Cyclodextrins/*chemistry/metabolism, Glucans/chemistry, Glucose/pharmacology, Glycogen Phosphorylase, Muscle Form/*chemistry, Glycogen/chemistry, Hydrogen Bonding, Kinetics, Models, Chemical, Oligosaccharides/chemistry, Phosphorylation, Protein Binding, Protein Structure, Tertiary, Rabbits},
	isbn = {0961-8368 (Print)1469-896X (Electronic)0961-8368 (Linking)},
	author = {Pinotsis, N. and Leonidas, D D and Chrysina, E D and Oikonomakos, N G and Mavridis, I. M.}
}
