6zqz - Revision history

OCA at 11:56, 1 February 2024

OCA — Thu, 01 Feb 2024 11:56:39 GMT

←Older revision		Revision as of 11:56, 1 February 2024
Line 3:		Line 3:
	<StructureSection load='6zqz' size='340' side='right'caption='[[6zqz]], [[Resolution\|resolution]] 1.88Å' scene=''>		<StructureSection load='6zqz' size='340' side='right'caption='[[6zqz]], [[Resolution\|resolution]] 1.88Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6zqz]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZQZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6ZQZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6zqz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZQZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZQZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=QOQ:5-[bis(fluoranyl)methyl]-7-[(3~{S})-1-[(2-chloranyl-6-methyl-pyridin-4-yl)methyl]piperidin-3-yl]-[1,2,4]triazolo[1,5-a]pyrimidine'>QOQ</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]] 1.88Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDE2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=QOQ:5-[bis(fluoranyl)methyl]-7-[(3~{S})-1-[(2-chloranyl-6-methyl-pyridin-4-yl)methyl]piperidin-3-yl]-[1,2,4]triazolo[1,5-a]pyrimidine'>QOQ</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] </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=6zqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zqz OCA], [https://pdbe.org/6zqz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zqz RCSB], [https://www.ebi.ac.uk/pdbsum/6zqz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zqz ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6zqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zqz OCA], [~~http~~://pdbe.org/6zqz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6zqz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6zqz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6zqz ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PDE2A_HUMAN PDE2A_HUMAN]] Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.<ref>PMID:15938621</ref> <ref>PMID:19828435</ref>	+	[https://www.uniprot.org/uniprot/PDE2A_HUMAN PDE2A_HUMAN] Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.<ref>PMID:15938621</ref> <ref>PMID:19828435</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~3',5'-cyclic-nucleotide phosphodiesterase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Leonard~~, P M~~]]	+	[[Category: Leonard PM]]
-	[[Category: Tresadern, G]]	+	[[Category: Tresadern G]]
-	~~[[Category: Alzheimers disease]]~~	+
-	~~[[Category: Binding free energy]]~~	+
-	~~[[Category: Fep]]~~	+
-	~~[[Category: Free energy perturbation]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Molecular design]]~~	+
-	~~[[Category: Molecular dynamic]]~~	+
-	~~[[Category: Pde2a inhibitor]]~~	+
-	~~[[Category: Phosphodiesterase]]~~	+
-	~~[[Category: Sbdd~~]]	+

OCA at 07:15, 25 November 2020

OCA — Wed, 25 Nov 2020 07:15:17 GMT

←Older revision		Revision as of 07:15, 25 November 2020
Line 1:		Line 1:

	==[1,2,4]Triazolo[1,5-a]pyrimidine Phosphodiesterase 2 Inhibitors==		==[1,2,4]Triazolo[1,5-a]pyrimidine Phosphodiesterase 2 Inhibitors==
-	<StructureSection load='6zqz' size='340' side='right'caption='[[6zqz]]' scene=''>	+	<StructureSection load='6zqz' size='340' side='right'caption='[[6zqz]], [[Resolution\|resolution]] 1.88Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZQZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ZQZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6zqz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZQZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ZQZ FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6zqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zqz OCA], [http://pdbe.org/6zqz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6zqz RCSB], [http://www.ebi.ac.uk/pdbsum/6zqz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6zqz ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=QOQ:5-[bis(fluoranyl)methyl]-7-[(3~{S})-1-[(2-chloranyl-6-methyl-pyridin-4-yl)methyl]piperidin-3-yl]-[1,2,4]triazolo[1,5-a]pyrimidine'>QOQ</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">PDE2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6zqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zqz OCA], [http://pdbe.org/6zqz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6zqz RCSB], [http://www.ebi.ac.uk/pdbsum/6zqz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6zqz ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PDE2A_HUMAN PDE2A_HUMAN]] Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.<ref>PMID:15938621</ref> <ref>PMID:19828435</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We describe the hit-to-lead exploration of a [1,2,4]triazolo[1,5-a]pyrimidine phosphodiesterase 2A (PDE2A) inhibitor arising from high-throughput screening. X-ray crystallography enabled structure-guided design, leading to the identification of preferred substructural components. Further rounds of optimization used relative binding free-energy calculations to prioritize different substituents from the large accessible chemical space. The free-energy perturbation (FEP) calculations were performed for 265 putative PDE2A inhibitors, and 100 compounds were synthesized representing a relatively large prospective application providing unexpectedly active molecules with IC50's from 2340 to 0.89 nM. Lead compound 46 originating from the FEP calculations showed PDE2A inhibition IC50 of 1.3 +/- 0.39 nM, approximately 100-fold selectivity versus other PDE enzymes, clean cytochrome P450 profile, in vivo target occupancy, and promise for further lead optimization.
		+
		+	[1,2,4]Triazolo[1,5-a]pyrimidine Phosphodiesterase 2A Inhibitors: Structure and Free-Energy Perturbation-Guided Exploration.,Tresadern G, Velter I, Trabanco AA, Van den Keybus F, Macdonald GJ, Somers MVF, Vanhoof G, Leonard PM, Lamers MBAC, Van Roosbroeck YEM, Buijnsters PJJA J Med Chem. 2020 Oct 26. doi: 10.1021/acs.jmedchem.0c01272. PMID:33105987<ref>PMID:33105987</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6zqz" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Leonard PM]]	+	[[Category: Leonard, P M]]
-	[[Category: Tresadern G]]	+	[[Category: Tresadern, G]]
		+	[[Category: Alzheimers disease]]
		+	[[Category: Binding free energy]]
		+	[[Category: Fep]]
		+	[[Category: Free energy perturbation]]
		+	[[Category: Hydrolase]]
		+	[[Category: Molecular design]]
		+	[[Category: Molecular dynamic]]
		+	[[Category: Pde2a inhibitor]]
		+	[[Category: Phosphodiesterase]]
		+	[[Category: Sbdd]]

OCA at 07:25, 4 November 2020

OCA — Wed, 04 Nov 2020 07:25:03 GMT

←Older revision		Revision as of 07:25, 4 November 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6zqz is ON HOLD until Paper Publication~~	+	==[1,2,4]Triazolo[1,5-a]pyrimidine Phosphodiesterase 2 Inhibitors==
-		+	<StructureSection load='6zqz' size='340' side='right'caption='[[6zqz]]' scene=''>
-	~~Authors: Tresadern, G., Leonard, P.M.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZQZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ZQZ FirstGlance]. <br>
-	~~Description:~~ [1,2,4]Triazolo[1,5-a]pyrimidine Phosphodiesterase 2 Inhibitors	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6zqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zqz OCA], [http://pdbe.org/6zqz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6zqz RCSB], [http://www.ebi.ac.uk/pdbsum/6zqz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6zqz ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Tresadern, G~~]]	+	__TOC__
-	[[Category: ~~Leonard, P.M~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Leonard PM]]
		+	[[Category: Tresadern G]]

OCA: Protected "6zqz" [edit=sysop:move=sysop]

OCA — Wed, 22 Jul 2020 08:14:55 GMT

Protected "6zqz" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:14, 22 July 2020

OCA: New page: '''Unreleased structure''' The entry 6zqz is ON HOLD until Paper Publication Authors: Tresadern, G., Leonard, P.M. Description: [1,2,4]Triazolo[1,5-a]pyrimidine Phosphodiesterase 2 Inh...

OCA — Wed, 22 Jul 2020 08:14:53 GMT

New page: '''Unreleased structure''' The entry 6zqz is ON HOLD until Paper Publication Authors: Tresadern, G., Leonard, P.M. Description: [1,2,4]Triazolo[1,5-a]pyrimidine Phosphodiesterase 2 Inh...

New page

'''Unreleased structure'''

The entry 6zqz is ON HOLD until Paper Publication

Authors: Tresadern, G., Leonard, P.M.

Description: [1,2,4]Triazolo[1,5-a]pyrimidine Phosphodiesterase 2 Inhibitors
[[Category: Unreleased Structures]]
[[Category: Tresadern, G]]
[[Category: Leonard, P.M]]