5c1w - Revision history

OCA at 12:18, 6 March 2024

OCA — Wed, 06 Mar 2024 12:18:35 GMT

←Older revision		Revision as of 12:18, 6 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5c1w]] 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=5C1W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5C1W FirstGlance]. <br>		<table><tr><td colspan='2'>[[5c1w]] 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=5C1W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5C1W FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4XS:4,6-DICHLORO-2-CYCLOPROPYL-5-METHYLPYRIMIDINE'>4XS</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]] 1.7Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4XS:4,6-DICHLORO-2-CYCLOPROPYL-5-METHYLPYRIMIDINE'>4XS</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=5c1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c1w OCA], [https://pdbe.org/5c1w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5c1w RCSB], [https://www.ebi.ac.uk/pdbsum/5c1w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5c1w 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=5c1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c1w OCA], [https://pdbe.org/5c1w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5c1w RCSB], [https://www.ebi.ac.uk/pdbsum/5c1w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5c1w ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>		[https://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Screening of a fragment library for PDE10A inhibitors identified a low molecular weight pyrimidine hit with PDE10A Ki of 8700 nM and LE of 0.59. Initial optimization by catalog followed by iterative parallel synthesis guided by X-ray cocrystal structures resulted in rapid potency improvements with minimal loss of ligand efficiency. Compound 15h, with PDE10A Ki of 8.2 pM, LE of 0.49, and >5000-fold selectivity over other PDEs, fully attenuates MK-801-induced hyperlocomotor activity after ip dosing.
-
-	Discovery and Optimization of a Series of Pyrimidine-Based Phosphodiesterase 10A (PDE10A) Inhibitors through Fragment Screening, Structure-Based Design, and Parallel Synthesis.,Shipe WD, Sharik SS, Barrow JC, McGaughey GB, Theberge CR, Uslaner JM, Yan Y, Renger JJ, Smith SM, Coleman PJ, Cox CD J Med Chem. 2015 Sep 25. PMID:26378882<ref>PMID:26378882</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5c1w" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 06:16, 7 June 2023

OCA — Wed, 07 Jun 2023 06:16:38 GMT

←Older revision		Revision as of 06:16, 7 June 2023
Line 3:		Line 3:
	<StructureSection load='5c1w' size='340' side='right'caption='[[5c1w]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='5c1w' size='340' side='right'caption='[[5c1w]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5c1w]] 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=5C1W OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5C1W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5c1w]] 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=5C1W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5C1W FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4XS:4,6-DICHLORO-2-CYCLOPROPYL-5-METHYLPYRIMIDINE'>4XS</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=4XS:4,6-DICHLORO-2-CYCLOPROPYL-5-METHYLPYRIMIDINE'>4XS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5c28\|5c28]], [[5c29\|5c29]], [[5c2a\|5c2a]], [[5c2e\|5c2e]], [[5c2h\|5c2h]]</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=5c1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c1w OCA], [https://pdbe.org/5c1w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5c1w RCSB], [https://www.ebi.ac.uk/pdbsum/5c1w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5c1w ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDE10A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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=5c1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c1w OCA], [~~http~~://pdbe.org/5c1w PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5c1w RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5c1w PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5c1w ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN]] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>	+	[https://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Yan, Y]]	+	[[Category: Yan Y]]
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Phosphodiesterase~~]]	+

OCA at 11:08, 18 March 2020

OCA — Wed, 18 Mar 2020 11:08:34 GMT

←Older revision		Revision as of 11:08, 18 March 2020
Line 1:		Line 1:
		+
	==PDE10 complexed with 4,6-dichloro-2-cyclopropyl-5-methyl-pyrimidine==		==PDE10 complexed with 4,6-dichloro-2-cyclopropyl-5-methyl-pyrimidine==
-	<StructureSection load='5c1w' size='340' side='right' caption='[[5c1w]], [[Resolution\|resolution]] 1.70Å' scene=''>	+	<StructureSection load='5c1w' size='340' side='right'caption='[[5c1w]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5c1w]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C1W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5C1W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5c1w]] 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=5C1W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5C1W FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4XS:4,6-DICHLORO-2-CYCLOPROPYL-5-METHYLPYRIMIDINE'>4XS</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=4XS:4,6-DICHLORO-2-CYCLOPROPYL-5-METHYLPYRIMIDINE'>4XS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5c28\|5c28]], [[5c29\|5c29]], [[5c2a\|5c2a]], [[5c2e\|5c2e]], [[5c2h\|5c2h]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5c28\|5c28]], [[5c29\|5c29]], [[5c2a\|5c2a]], [[5c2e\|5c2e]], [[5c2h\|5c2h]]</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=5c1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c1w OCA], [http://pdbe.org/5c1w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5c1w RCSB], [http://www.ebi.ac.uk/pdbsum/5c1w PDBsum]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDE10A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5c1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c1w OCA], [http://pdbe.org/5c1w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5c1w RCSB], [http://www.ebi.ac.uk/pdbsum/5c1w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5c1w ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5c1w" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5c1w" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphodiesterase 3D structures\|Phosphodiesterase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Yan, Y]]		[[Category: Yan, Y]]
	[[Category: Complex]]		[[Category: Complex]]

OCA at 14:30, 30 September 2015

OCA — Wed, 30 Sep 2015 14:30:13 GMT

←Older revision		Revision as of 14:30, 30 September 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==PDE10 complexed with 4,6-dichloro-2-cyclopropyl-5-methyl-pyrimidine==
		+	<StructureSection load='5c1w' size='340' side='right' caption='[[5c1w]], [[Resolution\|resolution]] 1.70Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5c1w]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C1W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5C1W FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4XS:4,6-DICHLORO-2-CYCLOPROPYL-5-METHYLPYRIMIDINE'>4XS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5c28\|5c28]], [[5c29\|5c29]], [[5c2a\|5c2a]], [[5c2e\|5c2e]], [[5c2h\|5c2h]]</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=5c1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c1w OCA], [http://pdbe.org/5c1w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5c1w RCSB], [http://www.ebi.ac.uk/pdbsum/5c1w PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN]] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Screening of a fragment library for PDE10A inhibitors identified a low molecular weight pyrimidine hit with PDE10A Ki of 8700 nM and LE of 0.59. Initial optimization by catalog followed by iterative parallel synthesis guided by X-ray cocrystal structures resulted in rapid potency improvements with minimal loss of ligand efficiency. Compound 15h, with PDE10A Ki of 8.2 pM, LE of 0.49, and >5000-fold selectivity over other PDEs, fully attenuates MK-801-induced hyperlocomotor activity after ip dosing.

-	~~The entry 5c1w is ON HOLD until Paper Publication~~	+	Discovery and Optimization of a Series of Pyrimidine-Based Phosphodiesterase 10A (PDE10A) Inhibitors through Fragment Screening, Structure-Based Design, and Parallel Synthesis.,Shipe WD, Sharik SS, Barrow JC, McGaughey GB, Theberge CR, Uslaner JM, Yan Y, Renger JJ, Smith SM, Coleman PJ, Cox CD J Med Chem. 2015 Sep 25. PMID:26378882<ref>PMID:26378882</ref>

-	~~Authors: Yan~~, Y.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~:	+	<div class="pdbe-citations 5c1w" style="background-color:#fffaf0;"></div>
-	~~[[Category: Unreleased Structures]]~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Yan, Y]]		[[Category: Yan, Y]]
		+	[[Category: Complex]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Phosphodiesterase]]

OCA at 12:05, 15 July 2015

OCA — Wed, 15 Jul 2015 12:05:59 GMT

←Older revision		Revision as of 12:05, 15 July 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5c1w is ON HOLD	+	The entry 5c1w is ON HOLD until Paper Publication

	Authors: Yan, Y.		Authors: Yan, Y.

OCA: Protected "5c1w" [edit=sysop:move=sysop]

OCA — Wed, 24 Jun 2015 11:56:51 GMT

Protected "5c1w" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:56, 24 June 2015

OCA: New page: '''Unreleased structure''' The entry 5c1w is ON HOLD Authors: Yan, Y. Description: Category: Unreleased Structures Category: Yan, Y

OCA — Wed, 24 Jun 2015 11:56:50 GMT

New page: '''Unreleased structure''' The entry 5c1w is ON HOLD Authors: Yan, Y. Description: Category: Unreleased Structures Category: Yan, Y

New page

'''Unreleased structure'''

The entry 5c1w is ON HOLD

Authors: Yan, Y.

Description:
[[Category: Unreleased Structures]]
[[Category: Yan, Y]]