4qge - Revision history

OCA at 06:52, 3 April 2024

OCA — Wed, 03 Apr 2024 06:52:02 GMT

←Older revision		Revision as of 06:52, 3 April 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<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>		<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" 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>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2Å</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='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'>[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>
	</table>		</table>
	== 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.
-
-	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>
-	<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>

OCA at 11:29, 15 February 2023

OCA — Wed, 15 Feb 2023 11:29:05 GMT

←Older revision		Revision as of 11:29, 15 February 2023
Line 3:		Line 3:
	<StructureSection load='4qge' size='340' side='right'caption='[[4qge]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4qge' size='340' side='right'caption='[[4qge]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== 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>		</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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 20:

	==See Also==		==See Also==
-	*[[Phosphodiesterase\|Phosphodiesterase]]	+	*[[Phosphodiesterase 3D structures\|Phosphodiesterase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Chimpansee troglodytes]]
	[[Category: Large Structures]]		[[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~~]]	+

OCA at 09:21, 24 April 2019

OCA — Wed, 24 Apr 2019 09:21:48 GMT

←Older revision		Revision as of 09:21, 24 April 2019
Line 1:		Line 1:

	==phosphodiesterase-9A in complex with inhibitor WYQ-C36D==		==phosphodiesterase-9A in complex with inhibitor WYQ-C36D==
-	<StructureSection load='4qge' size='340' side='right' caption='[[4qge]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='4qge' size='340' side='right'caption='[[4qge]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== 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>	+	<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>
	</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"><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'>[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>		<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>		</table>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Chimpansee troglodytes]]
		+	[[Category: Large Structures]]
	[[Category: Cui, W]]		[[Category: Cui, W]]
	[[Category: Huang, M]]		[[Category: Huang, M]]

OCA at 20:10, 11 August 2016

OCA — Thu, 11 Aug 2016 20:10:34 GMT

←Older revision		Revision as of 20:10, 11 August 2016
Line 1:		Line 1:
		+
	==phosphodiesterase-9A in complex with inhibitor WYQ-C36D==		==phosphodiesterase-9A in complex with inhibitor WYQ-C36D==
	<StructureSection load='4qge' size='340' side='right' caption='[[4qge]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4qge' size='340' side='right' caption='[[4qge]], [[Resolution\|resolution]] 2.00Å' scene=''>
Line 4:		Line 5:
	<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>		<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>		</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>	+	<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>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 14:		Line 15:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4qge" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphodiesterase\|Phosphodiesterase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 16:06, 10 December 2014

OCA — Wed, 10 Dec 2014 16:06:31 GMT

←Older revision		Revision as of 16:06, 10 December 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==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.

-	~~The entry 4qge is ON HOLD~~	+	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>

-	~~Authors: Shao~~, Y.-X.~~, Huang, M~~., Cui, W., Ke, H.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~phosphodiesterase~~-~~9A in complex with~~ inhibitor ~~WYQ-C36D~~	+	== 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]]

OCA at 05:53, 25 June 2014

OCA — Wed, 25 Jun 2014 05:53:53 GMT

←Older revision		Revision as of 05:53, 25 June 2014
Line 3:		Line 3:
	The entry 4qge is ON HOLD		The entry 4qge is ON HOLD

-	Authors: Shao, ~~Yong~~-~~xian~~, Huang, ~~Manna~~ , Cui, ~~Wenjun~~, Ke, ~~Hengming~~	+	Authors: Shao, Y.-X., Huang, M., Cui, W., Ke, H.

	Description: phosphodiesterase-9A in complex with inhibitor WYQ-C36D		Description: phosphodiesterase-9A in complex with inhibitor WYQ-C36D

OCA: Protected "4qge" [edit=sysop:move=sysop]

OCA — Wed, 28 May 2014 08:35:14 GMT

Protected "4qge" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:35, 28 May 2014

OCA: New page: '''Unreleased structure''' The entry 4qge is ON HOLD Authors: Shao, Yong-xian, Huang, Manna , Cui, Wenjun, Ke, Hengming Description: phosphodiesterase-9A in complex with inhibitor WYQ-...

OCA — Wed, 28 May 2014 08:35:12 GMT

New page: '''Unreleased structure''' The entry 4qge is ON HOLD Authors: Shao, Yong-xian, Huang, Manna , Cui, Wenjun, Ke, Hengming Description: phosphodiesterase-9A in complex with inhibitor WYQ-...

New page

'''Unreleased structure'''

The entry 4qge is ON HOLD

Authors: Shao, Yong-xian, Huang, Manna , Cui, Wenjun, Ke, Hengming

Description: phosphodiesterase-9A in complex with inhibitor WYQ-C36D