1exv | pdb_00001exv

HUMAN LIVER GLYCOGEN PHOSPHORYLASE A COMPLEXED WITH GLCNAC AND CP-403,700

spinqualitylabelsall models 1exv, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1exv is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 700, MPD, NBG, PLP Activity: Phosphorylase, with EC number 2.4.1.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [PYGL_HUMAN] Defects in PYGL are the cause of glycogen storage disease type 6 (GSD6) [MIM:232700]. A metabolic disorder characterized by mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected. Function [PYGL_HUMAN] Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Background: Glycogen phosphorylases catalyze the breakdown of glycogen to glucose-1-phosphate for glycolysis. Maintaining control of blood glucose levels is critical in minimizing the debilitating effects of diabetes, making liver glycogen phosphorylase a potential therapeutic target.Results: The binding site in human liver glycogen phosphorylase (HLGP) for a class of promising antidiabetic agents was identified crystallographically. The site is novel and functions allosterically by stabilizing the inactive conformation of HLGP. The initial view of the complex revealed key structural information and inspired the design of a new class of inhibitors which bind with nanomolar affinity and whose crystal structure is also described. Conclusions: We have identified the binding site of a new class of allosteric HLGP inhibitors. The crystal structure revealed the details of inhibitor binding, led to the design of a new class of compounds, and should accelerate efforts to develop therapeutically relevant molecules for the treatment of diabetes. Human liver glycogen phosphorylase inhibitors bind at a new allosteric site.,Rath VL, Ammirati M, Danley DE, Ekstrom JL, Gibbs EM, Hynes TR, Mathiowetz AM, McPherson RK, Olson TV, Treadway JL, Hoover DJ Chem Biol. 2000 Sep;7(9):677-82. PMID:10980448 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glycogen phosphorylase 3D structures

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