3tvx - Revision history

OCA at 13:41, 14 March 2024

OCA — Thu, 14 Mar 2024 13:41:17 GMT

←Older revision		Revision as of 13:41, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3tvx' size='340' side='right'caption='[[3tvx]], [[Resolution\|resolution]] 2.84Å' scene=''>		<StructureSection load='3tvx' size='340' side='right'caption='[[3tvx]], [[Resolution\|resolution]] 2.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tvx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TVX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tvx]] is a 2 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=3TVX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TVX 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=PNX:3,7-DIMETHYL-1-(5-OXOHEXYL)-3,7-DIHYDRO-1H-PURINE-2,6-DIONE'>PNX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.84Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDE4A, DPDE2 ([https://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=PNX:3,7-DIMETHYL-1-(5-OXOHEXYL)-3,7-DIHYDRO-1H-PURINE-2,6-DIONE'>PNX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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'>[https://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [https://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=3tvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvx OCA], [https://pdbe.org/3tvx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tvx RCSB], [https://www.ebi.ac.uk/pdbsum/3tvx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tvx 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=3tvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvx OCA], [https://pdbe.org/3tvx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tvx RCSB], [https://www.ebi.ac.uk/pdbsum/3tvx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tvx ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/PDE4A_HUMAN PDE4A_HUMAN]] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:11566027</ref> <ref>PMID:17727341</ref>	+	[https://www.uniprot.org/uniprot/PDE4A_HUMAN PDE4A_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:11566027</ref> <ref>PMID:17727341</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Fragment-based screening has typically relied on X-ray or nuclear magnetic resonance methods to identify low-affinity ligands that bind to therapeutic targets. These techniques are expensive in terms of material and time, so it useful to have a higher throughput method to reliably prescreen a fragment library to identify a subset of compounds for structural analysis. Calorimetry provides a label-free method to assay binding and enzymatic activity that is unaffected by the spectroscopic properties of the sample. Conventional microcalorimetry is hampered by requiring large quantities of reagents and long measurement times. Nanocalorimeters can overcome these limitations of conventional isothermal titration calorimetry. Here we have used enthalpy arrays, which are arrays of nanocalorimeters, to perform an enzyme activity-based fragment screen for competitive inhibitors of phosphodiesterase 4A (PDE4A). Several inhibitors with KI <2 mM were identified and moved to X-ray crystallization trials. Although the co-crystals did not yield high-resolution data, evidence of binding was observed, and the chemical structures of the hits were consistent with motifs of known PDE4 inhibitors. This study shows how array calorimetry can be used as a prescreening method for fragment-based lead discovery with enzyme targets and provides a list of candidate fragments for inhibition of PDE4A.	+
-		+
-	Fragment-Based Screening for Inhibitors of PDE4A Using Enthalpy Arrays and X-ray Crystallography.,Recht MI, Sridhar V, Badger J, Hernandez L, Chie-Leon B, Nienaber V, Torres FE J Biomol Screen. 2012 Jan 5. PMID:22223051<ref>PMID:22223051</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3tvx" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 27:		Line 17:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~3',5'-cyclic-nucleotide phosphodiesterase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Badger, J]]	+	[[Category: Badger J]]
-	[[Category: Sridhar, V]]	+	[[Category: Sridhar V]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex~~]]	+

OCA at 05:47, 13 July 2022

OCA — Wed, 13 Jul 2022 05:47:36 GMT

←Older revision		Revision as of 05:47, 13 July 2022
Line 1:		Line 1:

	==The structure of PDE4A with pentoxifylline at 2.84A resolution==		==The structure of PDE4A with pentoxifylline at 2.84A resolution==
-	<StructureSection load='3tvx' size='340' side='right' caption='[[3tvx]], [[Resolution\|resolution]] 2.84Å' scene=''>	+	<StructureSection load='3tvx' size='340' side='right'caption='[[3tvx]], [[Resolution\|resolution]] 2.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tvx]] is a 2 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=3TVX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3TVX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tvx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TVX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PNX:3,7-DIMETHYL-1-(5-OXOHEXYL)-3,7-DIHYDRO-1H-PURINE-2,6-DIONE'>PNX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PNX:3,7-DIMETHYL-1-(5-OXOHEXYL)-3,7-DIHYDRO-1H-PURINE-2,6-DIONE'>PNX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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">PDE4A, DPDE2 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDE4A, DPDE2 ([https://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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [https://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~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3tvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvx OCA], [~~http~~://pdbe.org/3tvx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3tvx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3tvx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3tvx 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=3tvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvx OCA], [https://pdbe.org/3tvx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tvx RCSB], [https://www.ebi.ac.uk/pdbsum/3tvx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tvx ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/PDE4A_HUMAN PDE4A_HUMAN]] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:11566027</ref> <ref>PMID:17727341</ref>	+	[[https://www.uniprot.org/uniprot/PDE4A_HUMAN PDE4A_HUMAN]] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:11566027</ref> <ref>PMID:17727341</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 22:

	==See Also==		==See Also==
-	*[[Phosphodiesterase\|Phosphodiesterase]]	+	*[[Phosphodiesterase 3D structures\|Phosphodiesterase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 29:		Line 29:
	[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]		[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Badger, J]]		[[Category: Badger, J]]
	[[Category: Sridhar, V]]		[[Category: Sridhar, V]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 13:57, 5 August 2016

OCA — Fri, 05 Aug 2016 13:57:40 GMT

←Older revision		Revision as of 13:57, 5 August 2016
Line 1:		Line 1:
		+
	==The structure of PDE4A with pentoxifylline at 2.84A resolution==		==The structure of PDE4A with pentoxifylline at 2.84A resolution==
	<StructureSection load='3tvx' size='340' side='right' caption='[[3tvx]], [[Resolution\|resolution]] 2.84Å' scene=''>		<StructureSection load='3tvx' size='340' side='right' caption='[[3tvx]], [[Resolution\|resolution]] 2.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tvx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TVX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tvx]] is a 2 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=3TVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TVX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PNX:3,7-DIMETHYL-1-(5-OXOHEXYL)-3,7-DIHYDRO-1H-PURINE-2,6-DIONE'>PNX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PNX:3,7-DIMETHYL-1-(5-OXOHEXYL)-3,7-DIHYDRO-1H-PURINE-2,6-DIONE'>PNX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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">PDE4A, DPDE2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDE4A, DPDE2 ([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='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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tvx RCSB], [http://www.ebi.ac.uk/pdbsum/3tvx 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=3tvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvx OCA], [http://pdbe.org/3tvx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tvx RCSB], [http://www.ebi.ac.uk/pdbsum/3tvx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tvx ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 3tvx" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]		[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Badger, J]]		[[Category: Badger, J]]
	[[Category: Sridhar, V]]		[[Category: Sridhar, V]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 03:04, 25 December 2014

OCA — Thu, 25 Dec 2014 03:04:10 GMT

←Older revision		Revision as of 03:04, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3tvx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TVX FirstGlance]. <br>		<table><tr><td colspan='2'>[[3tvx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TVX FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PNX:3,7-DIMETHYL-1-(5-OXOHEXYL)-3,7-DIHYDRO-1H-PURINE-2,6-DIONE'>PNX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PNX:3,7-DIMETHYL-1-(5-OXOHEXYL)-3,7-DIHYDRO-1H-PURINE-2,6-DIONE'>PNX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDE4A, DPDE2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDE4A, DPDE2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-	<tr><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='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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tvx RCSB], [http://www.ebi.ac.uk/pdbsum/3tvx 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=3tvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tvx RCSB], [http://www.ebi.ac.uk/pdbsum/3tvx PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PDE4A_HUMAN PDE4A_HUMAN]] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:11566027</ref> <ref>PMID:17727341</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 14:		Line 16:
	Fragment-Based Screening for Inhibitors of PDE4A Using Enthalpy Arrays and X-ray Crystallography.,Recht MI, Sridhar V, Badger J, Hernandez L, Chie-Leon B, Nienaber V, Torres FE J Biomol Screen. 2012 Jan 5. PMID:22223051<ref>PMID:22223051</ref>		Fragment-Based Screening for Inhibitors of PDE4A Using Enthalpy Arrays and X-ray Crystallography.,Recht MI, Sridhar V, Badger J, Hernandez L, Chie-Leon B, Nienaber V, Torres FE J Biomol Screen. 2012 Jan 5. PMID:22223051<ref>PMID:22223051</ref>

-	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, 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>

Line 25:		Line 27:
	[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]		[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Badger, J.]]	+	[[Category: Badger, J]]
-	[[Category: Sridhar, V.]]	+	[[Category: Sridhar, V]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 06:35, 5 June 2014

OCA — Thu, 05 Jun 2014 06:35:26 GMT

←Older revision		Revision as of 06:35, 5 June 2014
Line 1:		Line 1:
-	[[~~Image:~~3tvx.~~png~~\|~~left~~\|~~200px~~]]	+	==The structure of PDE4A with pentoxifylline at 2.84A resolution==
		+	<StructureSection load='3tvx' size='340' side='right' caption='[[3tvx]], [[Resolution\|resolution]] 2.84Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3tvx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TVX FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PNX:3,7-DIMETHYL-1-(5-OXOHEXYL)-3,7-DIHYDRO-1H-PURINE-2,6-DIONE'>PNX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDE4A, DPDE2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tvx RCSB], [http://www.ebi.ac.uk/pdbsum/3tvx PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Fragment-based screening has typically relied on X-ray or nuclear magnetic resonance methods to identify low-affinity ligands that bind to therapeutic targets. These techniques are expensive in terms of material and time, so it useful to have a higher throughput method to reliably prescreen a fragment library to identify a subset of compounds for structural analysis. Calorimetry provides a label-free method to assay binding and enzymatic activity that is unaffected by the spectroscopic properties of the sample. Conventional microcalorimetry is hampered by requiring large quantities of reagents and long measurement times. Nanocalorimeters can overcome these limitations of conventional isothermal titration calorimetry. Here we have used enthalpy arrays, which are arrays of nanocalorimeters, to perform an enzyme activity-based fragment screen for competitive inhibitors of phosphodiesterase 4A (PDE4A). Several inhibitors with KI <2 mM were identified and moved to X-ray crystallization trials. Although the co-crystals did not yield high-resolution data, evidence of binding was observed, and the chemical structures of the hits were consistent with motifs of known PDE4 inhibitors. This study shows how array calorimetry can be used as a prescreening method for fragment-based lead discovery with enzyme targets and provides a list of candidate fragments for inhibition of PDE4A.

-	<!--	+	Fragment-Based Screening for Inhibitors of PDE4A Using Enthalpy Arrays and X-ray Crystallography.,Recht MI, Sridhar V, Badger J, Hernandez L, Chie-Leon B, Nienaber V, Torres FE J Biomol Screen. 2012 Jan 5. PMID:22223051<ref>PMID:22223051</ref>
-	~~The line below this paragraph~~, ~~containing "STRUCTURE_3tvx"~~, ~~creates the "Structure Box" on the page.~~	+
-	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~	+
-	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded)~~,	+
-	~~or leave the SCENE parameter empty for the default display.~~	+
-	-->	+
-	~~{{STRUCTURE_3tvx\| PDB=3tvx \| SCENE= }}~~	+

-	~~===The structure~~ of ~~PDE4A with pentoxifylline at 2~~.~~84A resolution===~~	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-		+	==See Also==
-	~~<!--~~	+	*[[Phosphodiesterase\|Phosphodiesterase]]
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_22223051}}, adds the Publication Abstract to the page~~	+	== References ==
-	~~(as it appears on PubMed at http://www.pubmed.gov), where 22223051 is the PubMed ID number.~~	+	<references/>
-	~~-->~~	+	__TOC__
-	~~{{ABSTRACT_PUBMED_22223051}}~~	+	</StructureSection>
-		+
-	==~~About this Structure~~==	+
-	[[~~3tvx~~]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVX OCA].	+
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:022223051<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]		[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 07:29, 1 February 2012

OCA — Wed, 01 Feb 2012 07:29:24 GMT

←Older revision		Revision as of 07:29, 1 February 2012
Line 1:		Line 1:
-	[[Image:3tvx.~~jpg~~\|left\|200px]]	+	[[Image:3tvx.png\|left\|200px]]

	<!--		<!--

OCA at 06:26, 25 January 2012

OCA — Wed, 25 Jan 2012 06:26:29 GMT

←Older revision		Revision as of 06:26, 25 January 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3tvx.jpg\|left\|200px]]

-	The ~~entry 3tvx~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3tvx", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3tvx\| PDB=3tvx \| SCENE= }}

-	~~Authors: Badger, J., Sridhar, V~~.	+	===The structure of PDE4A with pentoxifylline at 2.84A resolution===

-	~~Description:~~ The ~~structure of PDE4A with pentoxifylline~~ at 2.~~84A resolution~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22223051}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22223051 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22223051}}
		+
		+	==About this Structure==
		+	[[3tvx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVX OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022223051</ref><references group="xtra"/>
		+	[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
		+	[[Category: Homo sapiens]]
		+	[[Category: Badger, J.]]
		+	[[Category: Sridhar, V.]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 08:44, 30 October 2011

OCA — Sun, 30 Oct 2011 08:44:35 GMT

←Older revision		Revision as of 08:44, 30 October 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3tvx is ON HOLD	+	The entry 3tvx is ON HOLD until Paper Publication

	Authors: Badger, J., Sridhar, V.		Authors: Badger, J., Sridhar, V.

	Description: The structure of PDE4A with pentoxifylline at 2.84A resolution		Description: The structure of PDE4A with pentoxifylline at 2.84A resolution

OCA: Protected "3tvx" [edit=sysop:move=sysop]

OCA — Wed, 28 Sep 2011 05:18:40 GMT

Protected "3tvx" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:18, 28 September 2011

OCA: New page: '''Unreleased structure''' The entry 3tvx is ON HOLD Authors: Badger, J., Sridhar, V. Description: The structure of PDE4A with pentoxifylline at 2.84A resolution

OCA — Wed, 28 Sep 2011 05:18:39 GMT

New page: '''Unreleased structure''' The entry 3tvx is ON HOLD Authors: Badger, J., Sridhar, V. Description: The structure of PDE4A with pentoxifylline at 2.84A resolution

New page

'''Unreleased structure'''

The entry 3tvx is ON HOLD

Authors: Badger, J., Sridhar, V.

Description: The structure of PDE4A with pentoxifylline at 2.84A resolution