4qge
From Proteopedia
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== Function == | == 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] | [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 == | ||
| + | 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. | ||
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| + | 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> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4qge" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] | *[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
phosphodiesterase-9A in complex with inhibitor WYQ-C36D
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Categories: Large Structures | Pan troglodytes | Cui W | Huang M | Ke H | Shao Y-X
