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4qge

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Revision as of 11:29, 15 February 2023

phosphodiesterase-9A in complex with inhibitor WYQ-C36D

Structural highlights

4qge is a 2 chain structure with sequence from Pan troglodytes. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PDE9A_PANTR Specifically hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes. Highly specific: compared to other members of the cyclic nucleotide phosphodiesterase family, has the highest affinity and selectivity for cGMP. Specifically regulates natriuretic-peptide-dependent cGMP signaling in heart, acting as a regulator of cardiac hypertrophy in myocytes and muscle. Does not regulate nitric oxide-dependent cGMP in heart. Additional experiments are required to confirm whether its ability to hydrolyze natriuretic-peptide-dependent cGMP is specific to heart or is a general feature of the protein. In brain, involved in cognitive function, such as learning and long-term memory.[UniProtKB:O76083][UniProtKB:Q8QZV1]

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Shao YX, Huang M, Cui W, Feng LJ, Wu Y, Cai Y, Li Z, Zhu X, Liu P, Wan Y, Ke H, Luo HB. Discovery of a Phosphodiesterase 9A Inhibitor as a Potential Hypoglycemic Agent. J Med Chem. 2014 Dec 8. PMID:25432025 doi:http://dx.doi.org/10.1021/jm500836h

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4qge"

@@ Line 3: / Line 3: @@
 <StructureSection load='4qge' size='340' side='right'caption='[[4qge]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4qge]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Chimpansee_troglodytes Chimpansee troglodytes]. 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>
+<table><tr><td colspan='2'>[[4qge]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pan_troglodytes Pan troglodytes]. 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 [https://proteopedia.org/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>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDE9A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9598 Chimpansee troglodytes])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4qge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qge OCA], [https://pdbe.org/4qge PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qge RCSB], [https://www.ebi.ac.uk/pdbsum/4qge PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qge ProSAT]</span></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://pdbe.org/4qge PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qge RCSB], [http://www.ebi.ac.uk/pdbsum/4qge PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qge ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/PDE9A_PANTR PDE9A_PANTR] Specifically hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes. Highly specific: compared to other members of the cyclic nucleotide phosphodiesterase family, has the highest affinity and selectivity for cGMP. Specifically regulates natriuretic-peptide-dependent cGMP signaling in heart, acting as a regulator of cardiac hypertrophy in myocytes and muscle. Does not regulate nitric oxide-dependent cGMP in heart. Additional experiments are required to confirm whether its ability to hydrolyze natriuretic-peptide-dependent cGMP is specific to heart or is a general feature of the protein. In brain, involved in cognitive function, such as learning and long-term memory.[UniProtKB:O76083][UniProtKB:Q8QZV1]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 20: @@
 ==See Also==
-*[[Phosphodiesterase|Phosphodiesterase]]
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Chimpansee troglodytes]]
 [[Category: Large Structures]]
-[[Category: Cui, W]]
+[[Category: Pan troglodytes]]
-[[Category: Huang, M]]
+[[Category: Cui W]]
-[[Category: Ke, H]]
+[[Category: Huang M]]
-[[Category: Shao, Y X]]
+[[Category: Ke H]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
+[[Category: Shao Y-X]]
-[[Category: Pde9 catalytic domain]]

4qge

From Proteopedia

Revision as of 11:29, 15 February 2023

phosphodiesterase-9A in complex with inhibitor WYQ-C36D

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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