4muw - Revision history

OCA at 16:42, 20 September 2023

OCA — Wed, 20 Sep 2023 16:42:58 GMT

←Older revision		Revision as of 16:42, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4muw]] 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=4MUW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MUW FirstGlance]. <br>		<table><tr><td colspan='2'>[[4muw]] 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=4MUW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MUW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2F4:2-{4-[(6,7-DIFLUORO-1H-BENZIMIDAZOL-2-YL)AMINO]PHENOXY}-N-METHYL-3,4-BIPYRIDIN-2-AMINE'>2F4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.639Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2F4:2-{4-[(6,7-DIFLUORO-1H-BENZIMIDAZOL-2-YL)AMINO]PHENOXY}-N-METHYL-3,4-BIPYRIDIN-2-AMINE'>2F4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4muw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4muw OCA], [https://pdbe.org/4muw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4muw RCSB], [https://www.ebi.ac.uk/pdbsum/4muw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4muw 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=4muw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4muw OCA], [https://pdbe.org/4muw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4muw RCSB], [https://www.ebi.ac.uk/pdbsum/4muw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4muw ProSAT]</span></td></tr>
	</table>		</table>

OCA at 10:11, 28 December 2022

OCA — Wed, 28 Dec 2022 10:11:33 GMT

←Older revision		Revision as of 10:11, 28 December 2022
Line 1:		Line 1:

	==Crystal Structure of PDE10A with Novel Keto-Benzimidazole Inhibitor==		==Crystal Structure of PDE10A with Novel Keto-Benzimidazole Inhibitor==
-	<StructureSection load='4muw' size='340' side='right' caption='[[4muw]], [[Resolution\|resolution]] 2.64Å' scene=''>	+	<StructureSection load='4muw' size='340' side='right'caption='[[4muw]], [[Resolution\|resolution]] 2.64Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4muw]] 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=4MUW OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4MUW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4muw]] 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=4MUW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MUW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2F4:2-{4-[(6,7-DIFLUORO-1H-BENZIMIDAZOL-2-YL)AMINO]PHENOXY}-N-METHYL-3,4-BIPYRIDIN-2-AMINE'>2F4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=2F4:2-{4-[(6,7-DIFLUORO-1H-BENZIMIDAZOL-2-YL)AMINO]PHENOXY}-N-METHYL-3,4-BIPYRIDIN-2-AMINE'>2F4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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">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'>[https://proteopedia.org/fgij/fg.htm?mol=4muw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4muw OCA], [https://pdbe.org/4muw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4muw RCSB], [https://www.ebi.ac.uk/pdbsum/4muw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4muw 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=4muw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4muw OCA], [~~http~~://pdbe.org/4muw PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4muw RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4muw PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4muw 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 21:		Line 20:

	==See Also==		==See Also==
-	*[[Phosphodiesterase\|Phosphodiesterase]]	+	*[[Phosphodiesterase 3D structures\|Phosphodiesterase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Chmait, S~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Jordan,~~ S]]	+	[[Category: Chmait S]]
-	[[Category: ~~Hydrolase-hydrolase inhibitor complex]]~~	+	[[Category: Jordan S]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Keto-benzimidazole]]~~	+
-	~~[[Category: Pde10a]]~~	+
-	~~[[Category: Phosphodiesterase 10a~~]]	+

OCA at 01:16, 5 August 2016

OCA — Fri, 05 Aug 2016 01:16:02 GMT

←Older revision		Revision as of 01:16, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of PDE10A with Novel Keto-Benzimidazole Inhibitor==		==Crystal Structure of PDE10A with Novel Keto-Benzimidazole Inhibitor==
	<StructureSection load='4muw' size='340' side='right' caption='[[4muw]], [[Resolution\|resolution]] 2.64Å' scene=''>		<StructureSection load='4muw' size='340' side='right' caption='[[4muw]], [[Resolution\|resolution]] 2.64Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2F4:2-{4-[(6,7-DIFLUORO-1H-BENZIMIDAZOL-2-YL)AMINO]PHENOXY}-N-METHYL-3,4-BIPYRIDIN-2-AMINE'>2F4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=2F4:2-{4-[(6,7-DIFLUORO-1H-BENZIMIDAZOL-2-YL)AMINO]PHENOXY}-N-METHYL-3,4-BIPYRIDIN-2-AMINE'>2F4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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">PDE10A ([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">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=4muw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4muw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4muw RCSB], [http://www.ebi.ac.uk/pdbsum/4muw 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=4muw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4muw OCA], [http://pdbe.org/4muw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4muw RCSB], [http://www.ebi.ac.uk/pdbsum/4muw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4muw ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	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 4muw" style="background-color:#fffaf0;"></div>

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

OCA at 14:38, 25 December 2014

OCA — Thu, 25 Dec 2014 14:38:25 GMT

←Older revision		Revision as of 14:38, 25 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4muw\| PDB=4muw \| SCENE= }}~~	+	==Crystal Structure of PDE10A with Novel Keto-Benzimidazole Inhibitor==
-	===Crystal Structure of PDE10A with Novel Keto-Benzimidazole Inhibitor===	+	<StructureSection load='4muw' size='340' side='right' caption='[[4muw]], [[Resolution\|resolution]] 2.64Å' scene=''>
-	{~~{ABSTRACT_PUBMED_24102193}~~}	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4muw]] 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=4MUW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MUW FirstGlance]. <br>
-	==Function==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2F4:2-{4-[(6,7-DIFLUORO-1H-BENZIMIDAZOL-2-YL)AMINO]PHENOXY}-N-METHYL-3,4-BIPYRIDIN-2-AMINE'>2F4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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">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=4muw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4muw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4muw RCSB], [http://www.ebi.ac.uk/pdbsum/4muw 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>		[[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 ==
		+	Our development of PDE10A inhibitors began with an HTS screening hit (1) that exhibited both high p-glycoprotein (P-gp) efflux ratios in rat and human and poor metabolic stability. Based on co-crystal structure of 1 in human PDE10A enzyme, we designed a novel keto-benzimidazole 26 with comparable PDE10A potency devoid of efflux liabilities. On target in vivo coverage of PDE10A in rat brain was assessed using our previously reported LC-MS/MS receptor occupancy (RO) technology. Compound 26 achieved 55% RO of PDE10A at 30 mg/kg po and covered PDE10A receptors in rat brain in a dose-dependent manner. Co-crystal structure of 26 in PDE10A confirmed the binding mode of the novel scaffold. Further optimization resulted in the identification of keto-benzimidazole 34 which showed an increased in vivo efficacy of 57% RO in rats at 10 mg/kg po and an improved in vivo rat clearance and oral bioavailability.
		+
		+	Design, Optimization, and Biological Evaluation of Novel Keto-Benzimidazoles as Potent and Selective Inhibitors of Phosphodiesterase 10A (PDE10A).,Hu E, Kunz RK, Chen N, Rumfelt S, Siegmund A, Andrews K, Chmait S, Zhao S, Davis C, Chen H, Lester-Zeiner D, Ma J, Biorn C, Shi J, Porter A, Treanor J, Allen JR J Med Chem. 2013 Oct 8. PMID:24102193<ref>PMID:24102193</ref>

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4muw]] 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=4MUW OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:024102193</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Phosphodiesterase\|Phosphodiesterase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Chmait, S.]]	+	[[Category: Chmait, S]]
-	[[Category: Jordan, S.]]	+	[[Category: Jordan, S]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Inhibitor]]		[[Category: Inhibitor]]

OCA at 06:42, 15 January 2014

OCA — Wed, 15 Jan 2014 06:42:31 GMT

←Older revision		Revision as of 06:42, 15 January 2014
Line 7:		Line 7:

	==About this Structure==		==About this Structure==
-	[[4muw]] 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=4MUW OCA].	+	[[4muw]] 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=4MUW OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:024102193</ref><references group="xtra"/><references/>		<ref group="xtra">PMID:024102193</ref><references group="xtra"/><references/>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Chmait, S.]]		[[Category: Chmait, S.]]
	[[Category: Jordan, S.]]		[[Category: Jordan, S.]]

OCA at 06:41, 23 October 2013

OCA — Wed, 23 Oct 2013 06:41:46 GMT

←Older revision		Revision as of 06:41, 23 October 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4muw\| PDB=4muw \| SCENE= }}
		+	===Crystal Structure of PDE10A with Novel Keto-Benzimidazole Inhibitor===
		+	{{ABSTRACT_PUBMED_24102193}}

-	~~The entry 4muw~~ is ~~ON HOLD~~	+	==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>

-	~~Authors~~: ~~Chmait, S~~.~~, Jordan, S~~.	+	==About this Structure==
		+	[[4muw]] 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=4MUW OCA].

-	~~Description~~: ~~Crystal Structure of PDE10A with Novel Keto~~-~~Benzimidazole~~ Inhibitor	+	==Reference==
		+	<ref group="xtra">PMID:024102193</ref><references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Chmait, S.]]
		+	[[Category: Jordan, S.]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Keto-benzimidazole]]
		+	[[Category: Pde10a]]
		+	[[Category: Phosphodiesterase 10a]]

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

OCA — Wed, 02 Oct 2013 06:55:19 GMT

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

←Older revision

Revision as of 06:55, 2 October 2013

OCA: New page: '''Unreleased structure''' The entry 4muw is ON HOLD Authors: Chmait, S., Jordan, S. Description: Crystal Structure of PDE10A with Novel Keto-Benzimidazole Inhibitor

OCA — Wed, 02 Oct 2013 06:55:18 GMT

New page: '''Unreleased structure''' The entry 4muw is ON HOLD Authors: Chmait, S., Jordan, S. Description: Crystal Structure of PDE10A with Novel Keto-Benzimidazole Inhibitor

New page

'''Unreleased structure'''

The entry 4muw is ON HOLD

Authors: Chmait, S., Jordan, S.

Description: Crystal Structure of PDE10A with Novel Keto-Benzimidazole Inhibitor