4qge: Difference between revisions
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''' | ==phosphodiesterase-9A in complex with inhibitor WYQ-C36D== | ||
<StructureSection load='4qge' size='340' side='right' caption='[[4qge]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4qge]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QGE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QGE FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=35O:N~2~-(1-CYCLOPENTYL-4-OXO-4,7-DIHYDRO-1H-PYRAZOLO[3,4-D]PYRIMIDIN-6-YL)-N-(4-METHOXYPHENYL)-D-ALANINAMIDE'>35O</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qge OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qge RCSB], [http://www.ebi.ac.uk/pdbsum/4qge PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Phosphodiesterase 9 (PDE9) inhibitors have been studied as potential therapeutics for treatment of diabetes and Alzheimer's disease. Here we report a potent PDE9 inhibitor 3r that has an IC50 of 0.6 nM and >150-fold selectivity over other PDEs. The HepG2 cell-based assay shows that 3r inhibits the mRNA expression of phosphoenolpyruvate carboxykinase and glucose 6-phosphatase. These activities of 3r, together with the reasonable pharmacokinetic properties and no acute toxicity at 1200 mg/kg dosage, suggest its potential as a hypoglycemic agent. The crystal structure of PDE9-3r reveals significantly different conformation and hydrogen bonding pattern of 3r from those of previously published 28s. Both 3r and 28s form a hydrogen bond with Tyr424, a unique PDE9 residue (except for PDE8), but 3r shows an additional hydrogen bond with Ala452. This structure information might be useful for design of PDE9 inhibitors. | |||
Discovery of a Phosphodiesterase 9A Inhibitor as a Potential Hypoglycemic Agent.,Shao YX, Huang M, Cui W, Feng LJ, Wu Y, Cai Y, Li Z, Zhu X, Liu P, Wan Y, Ke H, Luo HB J Med Chem. 2014 Dec 8. PMID:25432025<ref>PMID:25432025</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Cui, W]] | |||
[[Category: Huang, M]] | |||
[[Category: Ke, H]] | |||
[[Category: Shao, Y X]] | |||
[[Category: Hydrolase-hydrolase inhibitor complex]] | |||
[[Category: Pde9 catalytic domain]] | |||
Revision as of 16:06, 10 December 2014
phosphodiesterase-9A in complex with inhibitor WYQ-C36D
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