1exv
From Proteopedia
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|PDB= 1exv |SIZE=350|CAPTION= <scene name='initialview01'>1exv</scene>, resolution 2.40Å | |PDB= 1exv |SIZE=350|CAPTION= <scene name='initialview01'>1exv</scene>, resolution 2.40Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=700:[5-CHLORO-1H-INDOL-2-CARBONYL-PHENYLALANINYL]-AZETIDINE-3-CARBOXYLIC+ACID'>700</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NBG:1-N-ACETYL-BETA-D-GLUCOSAMINE'>NBG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5'-PHOSPHATE'>PLP</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1exv|1EXV]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1exv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1exv OCA], [http://www.ebi.ac.uk/pdbsum/1exv PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1exv RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Glycogen storage disease VI OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=232700 232700]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Olson, T V.]] | [[Category: Olson, T V.]] | ||
[[Category: Rath, V L.]] | [[Category: Rath, V L.]] | ||
| - | [[Category: 700]] | ||
| - | [[Category: MPD]] | ||
| - | [[Category: NBG]] | ||
| - | [[Category: PLP]] | ||
[[Category: allosteric binding]] | [[Category: allosteric binding]] | ||
[[Category: allosteric site]] | [[Category: allosteric site]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:11:51 2008'' |
Revision as of 17:11, 30 March 2008
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| , resolution 2.40Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Activity: | Phosphorylase, with EC number 2.4.1.1 | ||||||
| Related: | 1EXV
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN LIVER GLYCOGEN PHOSPHORYLASE A COMPLEXED WITH GLCNAC AND CP-403,700
Overview
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.
About this Structure
1EXV is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Sun Mar 30 20:11:51 2008
