Sourcing the affinity of flavonoids for the glycogen phosphorylase inhibitor site via crystallography, kinetics and QM/MM-PBSA binding studies: Comparison of chrysin and flavopiridol

2013 ◽  
Vol 61 ◽  
pp. 14-27 ◽  
Author(s):  
Katerina E. Tsitsanou ◽  
Joseph M. Hayes ◽  
Maria Keramioti ◽  
Michalis Mamais ◽  
Nikos G. Oikonomakos ◽  
...  
Keyword(s):  
Glycogen Phosphorylase ◽  
Binding Studies ◽  
Glycogen Phosphorylase Inhibitor

ChemInform Abstract: Synthesis and Glycogen Phosphorylase Inhibitor Activity of Functionalized 1,4-Benzodioxanes.

ChemInform ◽  
2010 ◽  
Vol 41 (31) ◽  
pp. no-no
Author(s):  
Z. Czako ◽  
T. Docsa ◽  
P. Gergely ◽  
L. Luhasz ◽  
S. Antus
Keyword(s):  
Glycogen Phosphorylase ◽  
Inhibitor Activity ◽  
Glycogen Phosphorylase Inhibitor

Hepatic glycogen breakdown is implicated in the maintenance of plasma mannose concentration

2005 ◽  
Vol 288 (3) ◽  
pp. E534-E540 ◽  
Author(s):  
T. Taguchi ◽  
E. Yamashita ◽  
T. Mizutani ◽  
H. Nakajima ◽  
M. Yabuuchi ◽  
...  
Keyword(s):  
Glycogen Phosphorylase ◽  
Diabetic Rats ◽  
Hepatic Glycogen ◽  
Perfused Liver ◽  
Diabetes Model ◽  
Gluconeogenic Substrates ◽  
Glycogen Phosphorylase Inhibitor ◽  
Fasted Rats ◽  
Glycogen Breakdown

d-Mannose is an essential monosaccharide constituent of glycoproteins and glycolipids. However, it is unknown how plasma mannose is supplied. The aim of this study was to explore the source of plasma mannose. Oral administration of glucose resulted in a significant decrease of plasma mannose concentration after 20 min in fasted normal rats. However, in fasted type 2 diabetes model rats, plasma mannose concentrations that were higher compared with normal rats did not change after the administration of glucose. When insulin was administered intravenously to fed rats, it took longer for plasma mannose concentrations to decrease significantly in diabetic rats than in normal rats (20 and 5 min, respectively). Intravenous administration of epinephrine to fed normal rats increased the plasma mannose concentration, but this effect was negated by fasting or by administration of a glycogen phosphorylase inhibitor. Epinephrine increased mannose output from the perfused liver of fed rats, but this effect was negated in the presence of a glucose-6-phosphatase inhibitor. Epinephrine also increased the hepatic levels of hexose 6-phosphates, including mannose 6-phosphate. When either lactate alone or lactate plus alanine were administered as gluconeogenic substrates to fasted rats, the concentration of plasma mannose did not increase. When lactate was used to perfuse the liver of fasted rats, a decrease, rather than an increase, in mannose output was observed. These findings indicate that hepatic glycogen is a source of plasma mannose.

scholarly journals Allosteric interactions of glycogen phosphorylase b. A crystallographic study of glucose 6-phosphate and inorganic phosphate binding to di-imidate-cross-linked phosphorylase b

1984 ◽  
Vol 218 (1) ◽  
pp. 45-60 ◽  
Author(s):  
A Lorek ◽  
K S Wilson ◽  
M S P Sansom ◽  
D I Stuart ◽  
E A Stura ◽  
...  
Keyword(s):  
Binding Site ◽  
Conformational Changes ◽  
Inorganic Phosphate ◽  
Glycogen Phosphorylase ◽  
Phosphate Binding ◽  
Binding Studies ◽  
Structural Explanation ◽  
Alpha Helices ◽  
Allosteric Effector ◽  
Glycogen Phosphorylase B

The binding to glycogen phosphorylase b of glucose 6-phosphate and inorganic phosphate (respectively allosteric inhibitor and substrate/activator of the enzyme) were studied in the crystal at 0.3 nm (3A) resolution. Glucose 6-phosphate binds in the alpha-configuration at a site that is close to the AMP allosteric effector site at the subunit-subunit interface and promotes several conformational changes. The phosphate-binding site of the enzyme for glucose 6-phosphate involves contacts to two cationic residues, Arg-309 and Lys-247. This site is also occupied in the inorganic-phosphate-binding studies and is therefore identified as a high-affinity phosphate-binding site. It is distinct from the weaker phosphate-binding site of the enzyme for AMP, which is 0.27 nm (2.7A) away. The glucose moiety of glucose 6-phosphate and the adenosine moiety of AMP do not overlap. The results provide a structural explanation for the kinetic observations that glucose 6-phosphate inhibition of AMP activation of phosphorylase b is partially competitive and highly co-operative. The results suggest that the transmission of allosteric conformational changes involves an increase in affinity at phosphate-binding sites and relative movements of alpha-helices. In order to study glucose 6-phosphate and phosphate binding it was necessary to cross-link the crystals. The use of dimethyl malondi-imidate as a new cross-linking reagent in protein crystallography is discussed.

Cardioprotective effect of the glycogen phosphorylase inhibitor CP-380867

2001 ◽  
Vol 33 (6) ◽  
pp. A178 ◽  
Author(s):  
J.L. Treadway ◽  
W.P. Magee ◽  
D.J. Hoover ◽  
R.K. McPherson ◽  
W.H. Martin ◽  
...  
Keyword(s):  
Glycogen Phosphorylase ◽  
Cardioprotective Effect ◽  
Glycogen Phosphorylase Inhibitor

scholarly journals Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo

1998 ◽  
Vol 95 (4) ◽  
pp. 1776-1781 ◽  
Author(s):  
W. H. Martin ◽  
D. J. Hoover ◽  
S. J. Armento ◽  
I. A. Stock ◽  
R. K. McPherson ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Human Liver ◽  
Glycogen Phosphorylase ◽  
Liver Glycogen ◽  
Glycogen Phosphorylase Inhibitor

FR258900, a Novel Glycogen Phosphorylase Inhibitor Isolated from Fungus No.138354. Part 2. Antihyperglycemic Effects in Diabetic Animal Models.

ChemInform ◽  
2006 ◽  
Vol 37 (3) ◽  
Author(s):  
Shigetada Furukawa ◽  
Kana Murakami ◽  
Motoaki Nishikawa ◽  
Osamu Nakayama ◽  
Motohiro Hino
Keyword(s):  
Animal Models ◽  
Glycogen Phosphorylase ◽  
Diabetic Animal ◽  
Glycogen Phosphorylase Inhibitor
Sign in / Sign up

Export Citation Format

Share Document