1EXV: Human Liver Glycogen Phosphorylase A Complexed With Glcnac And Cp-403, 700

Citation:
Abstract
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.
PDB ID: 1EXVDownload
MMDB ID: 14719
PDB Deposition Date: 2000/5/4
Updated in MMDB: 2012/12
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
Similar Structures:
Biological Unit for 1EXV: dimeric; determined by author and by software (PISA)
Molecular Components in 1EXV
Label Count Molecule
Proteins (2 molecules)
2
Liver Glycogen Phosphorylase(Gene symbol: PYGL)
Molecule annotation
Chemicals (8 molecules)
1
2
2
2
3
2
4
2
* Click molecule labels to explore molecular sequence information.

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