3wka - Revision history

OCA at 19:22, 29 May 2024

OCA — Wed, 29 May 2024 19:22:13 GMT

←Older revision		Revision as of 19:22, 29 May 2024
Line 1:		Line 1:

	==Crystal structure of soluble epoxide hydrolase in complex with fragment inhibitor==		==Crystal structure of soluble epoxide hydrolase in complex with fragment inhibitor==
-	<StructureSection load='3wka' size='340' side='right'caption='[[3wka]]' scene=''>	+	<StructureSection load='3wka' size='340' side='right'caption='[[3wka]], [[Resolution\|resolution]] 2.01Å' 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=3WKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WKA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3wka]] is a 1 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=3WKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WKA FirstGlance]. <br>
-	</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=3wka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wka OCA], [https://pdbe.org/3wka PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wka RCSB], [https://www.ebi.ac.uk/pdbsum/3wka PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wka ProSAT]</span></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]] 2.01Å</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=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=S0G:6-AMINO-1-METHYL-5-(PIPERIDIN-1-YL)PYRIMIDINE-2,4(1H,3H)-DIONE'>S0G</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=3wka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wka OCA], [https://pdbe.org/3wka PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wka RCSB], [https://www.ebi.ac.uk/pdbsum/3wka PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wka ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/HYES_HUMAN HYES_HUMAN] Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and p-nitrophenyl phospate.<ref>PMID:12574508</ref> <ref>PMID:12574510</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Soluble epoxide hydrolase (sEH) is a component of the arachidonic acid cascade and is a candidate target for therapies for hypertension or inflammation. Although many sEH inhibitors are available, their scaffolds are not structurally diverse, and knowledge of their specific interactions with sEH is limited. To obtain detailed structural information about protein-ligand interactions, we conducted fragment screening of sEH, analyzed the fragments using high-throughput X-ray crystallography, and determined 126 fragment-bound structures at high resolution. Aminothiazole and benzimidazole derivatives were identified as novel scaffolds that bind to the catalytic triad of sEH with good ligand efficiency. We further identified fragment hits that bound to subpockets of sEH called the short and long branches. The water molecule conserved in the structure plays an important role in binding to the long branch, whereas Asp496 and the main chain of Phe497 form hydrogen bonds with fragment hits in the short branch. Fragment hits and their crystal structures provide structural insights into ligand binding to sEH that will facilitate the discovery of novel and potent inhibitors of sEH.
		+
		+	Structural insights into binding of inhibitors to soluble epoxide hydrolase gained by fragment screening and X-ray crystallography.,Amano Y, Yamaguchi T, Tanabe E Bioorg Med Chem. 2014 Apr 15;22(8):2427-34. doi: 10.1016/j.bmc.2014.03.001. Epub , 2014 Mar 12. PMID:24656800<ref>PMID:24656800</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 3wka" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Epoxide hydrolase 3D structures\|Epoxide hydrolase 3D structures]]		*[[Epoxide hydrolase 3D structures\|Epoxide hydrolase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Amano Y]]		[[Category: Amano Y]]
	[[Category: Tanabe E]]		[[Category: Tanabe E]]
	[[Category: Yamaguchi T]]		[[Category: Yamaguchi T]]

OCA at 10:33, 31 August 2022

OCA — Wed, 31 Aug 2022 10:33:46 GMT

←Older revision		Revision as of 10:33, 31 August 2022
Line 1:		Line 1:

	==Crystal structure of soluble epoxide hydrolase in complex with fragment inhibitor==		==Crystal structure of soluble epoxide hydrolase in complex with fragment inhibitor==
-	<StructureSection load='3wka' size='340' side='right'caption='[[3wka]]~~, [[Resolution\|resolution]] 2.01Å~~' scene=''>	+	<StructureSection load='3wka' size='340' side='right'caption='[[3wka]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>~~[[3wka]] is a 1 chain structure.~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WKA FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WKA 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=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=S0G:6-AMINO-1-METHYL-5-(PIPERIDIN-1-YL)PYRIMIDINE-2,4(1H,3H)-DIONE'>S0G</scene></td></tr>	+	</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=3wka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wka OCA], [https://pdbe.org/3wka PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wka RCSB], [https://www.ebi.ac.uk/pdbsum/3wka PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wka ProSAT]</span></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3wk4\|3wk4]], [[3wk5\|3wk5]], [[3wk6\|3wk6]], [[3wk7\|3wk7]], [[3wk8\|3wk8]], [[3wk9\|3wk9]], [[3wkb\|3wkb]], [[3wkc\|3wkc]], [[3wkd\|3wkd]], [[3wke\|3wke]]</div></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=3wka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wka OCA], [https://pdbe.org/3wka PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wka RCSB], [https://www.ebi.ac.uk/pdbsum/3wka PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wka ProSAT]</span></td></tr>	+
	</table>		</table>
-	== Function ==
-	[[https://www.uniprot.org/uniprot/HYES_HUMAN HYES_HUMAN]] Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and p-nitrophenyl phospate.<ref>PMID:12574508</ref> <ref>PMID:12574510</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Soluble epoxide hydrolase (sEH) is a component of the arachidonic acid cascade and is a candidate target for therapies for hypertension or inflammation. Although many sEH inhibitors are available, their scaffolds are not structurally diverse, and knowledge of their specific interactions with sEH is limited. To obtain detailed structural information about protein-ligand interactions, we conducted fragment screening of sEH, analyzed the fragments using high-throughput X-ray crystallography, and determined 126 fragment-bound structures at high resolution. Aminothiazole and benzimidazole derivatives were identified as novel scaffolds that bind to the catalytic triad of sEH with good ligand efficiency. We further identified fragment hits that bound to subpockets of sEH called the short and long branches. The water molecule conserved in the structure plays an important role in binding to the long branch, whereas Asp496 and the main chain of Phe497 form hydrogen bonds with fragment hits in the short branch. Fragment hits and their crystal structures provide structural insights into ligand binding to sEH that will facilitate the discovery of novel and potent inhibitors of sEH.
-
-	Structural insights into binding of inhibitors to soluble epoxide hydrolase gained by fragment screening and X-ray crystallography.,Amano Y, Yamaguchi T, Tanabe E Bioorg Med Chem. 2014 Apr 15;22(8):2427-34. doi: 10.1016/j.bmc.2014.03.001. Epub , 2014 Mar 12. PMID:24656800<ref>PMID:24656800</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 3wka" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Epoxide hydrolase 3D structures\|Epoxide hydrolase 3D structures]]		*[[Epoxide hydrolase 3D structures\|Epoxide hydrolase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Amano, Y]]	+	[[Category: Amano Y]]
-	[[Category: Tanabe, E]]	+	[[Category: Tanabe E]]
-	[[Category: Yamaguchi, T]]	+	[[Category: Yamaguchi T]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex~~]]	+

OCA at 04:58, 25 August 2022

OCA — Thu, 25 Aug 2022 04:58:20 GMT

←Older revision		Revision as of 04:58, 25 August 2022
Line 3:		Line 3:
	<StructureSection load='3wka' size='340' side='right'caption='[[3wka]], [[Resolution\|resolution]] 2.01Å' scene=''>		<StructureSection load='3wka' size='340' side='right'caption='[[3wka]], [[Resolution\|resolution]] 2.01Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3wka]] is a 1 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=3WKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WKA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3wka]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WKA 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=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=S0G:6-AMINO-1-METHYL-5-(PIPERIDIN-1-YL)PYRIMIDINE-2,4(1H,3H)-DIONE'>S0G</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=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=S0G:6-AMINO-1-METHYL-5-(PIPERIDIN-1-YL)PYRIMIDINE-2,4(1H,3H)-DIONE'>S0G</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3wk4\|3wk4]], [[3wk5\|3wk5]], [[3wk6\|3wk6]], [[3wk7\|3wk7]], [[3wk8\|3wk8]], [[3wk9\|3wk9]], [[3wkb\|3wkb]], [[3wkc\|3wkc]], [[3wkd\|3wkd]], [[3wke\|3wke]]</div></td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3wk4\|3wk4]], [[3wk5\|3wk5]], [[3wk6\|3wk6]], [[3wk7\|3wk7]], [[3wk8\|3wk8]], [[3wk9\|3wk9]], [[3wkb\|3wkb]], [[3wkc\|3wkc]], [[3wkd\|3wkd]], [[3wke\|3wke]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EPHX2 ([https://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=3wka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wka OCA], [https://pdbe.org/3wka PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wka RCSB], [https://www.ebi.ac.uk/pdbsum/3wka PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wka 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=3wka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wka OCA], [https://pdbe.org/3wka PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wka RCSB], [https://www.ebi.ac.uk/pdbsum/3wka PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wka ProSAT]</span></td></tr>
	</table>		</table>
Line 27:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Amano, Y]]		[[Category: Amano, Y]]

OCA at 05:39, 3 August 2022

OCA — Wed, 03 Aug 2022 05:39:52 GMT

←Older revision		Revision as of 05:39, 3 August 2022
Line 1:		Line 1:

	==Crystal structure of soluble epoxide hydrolase in complex with fragment inhibitor==		==Crystal structure of soluble epoxide hydrolase in complex with fragment inhibitor==
-	<StructureSection load='3wka' size='340' side='right' caption='[[3wka]], [[Resolution\|resolution]] 2.01Å' scene=''>	+	<StructureSection load='3wka' size='340' side='right'caption='[[3wka]], [[Resolution\|resolution]] 2.01Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3wka]] is a 1 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=3WKA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3WKA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3wka]] is a 1 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=3WKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WKA 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=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=S0G:6-AMINO-1-METHYL-5-(PIPERIDIN-1-YL)PYRIMIDINE-2,4(1H,3H)-DIONE'>S0G</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=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=S0G:6-AMINO-1-METHYL-5-(PIPERIDIN-1-YL)PYRIMIDINE-2,4(1H,3H)-DIONE'>S0G</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3wk4\|3wk4]], [[3wk5\|3wk5]], [[3wk6\|3wk6]], [[3wk7\|3wk7]], [[3wk8\|3wk8]], [[3wk9\|3wk9]], [[3wkb\|3wkb]], [[3wkc\|3wkc]], [[3wkd\|3wkd]], [[3wke\|3wke]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3wk4\|3wk4]], [[3wk5\|3wk5]], [[3wk6\|3wk6]], [[3wk7\|3wk7]], [[3wk8\|3wk8]], [[3wk9\|3wk9]], [[3wkb\|3wkb]], [[3wkc\|3wkc]], [[3wkd\|3wkd]], [[3wke\|3wke]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EPHX2 ([~~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">EPHX2 ([https://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=3wka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wka OCA], [~~http~~://pdbe.org/3wka PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3wka RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3wka PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3wka 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=3wka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wka OCA], [https://pdbe.org/3wka PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wka RCSB], [https://www.ebi.ac.uk/pdbsum/3wka PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wka ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/HYES_HUMAN HYES_HUMAN]] Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and p-nitrophenyl phospate.<ref>PMID:12574508</ref> <ref>PMID:12574510</ref>	+	[[https://www.uniprot.org/uniprot/HYES_HUMAN HYES_HUMAN]] Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and p-nitrophenyl phospate.<ref>PMID:12574508</ref> <ref>PMID:12574510</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==
-	*[[Epoxide hydrolase\|Epoxide hydrolase]]	+	*[[Epoxide hydrolase 3D structures\|Epoxide hydrolase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 28:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Amano, Y]]		[[Category: Amano, Y]]
	[[Category: Tanabe, E]]		[[Category: Tanabe, E]]

OCA at 08:11, 4 August 2016

OCA — Thu, 04 Aug 2016 08:11:13 GMT

←Older revision		Revision as of 08:11, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of soluble epoxide hydrolase in complex with fragment inhibitor==		==Crystal structure of soluble epoxide hydrolase in complex with fragment inhibitor==
	<StructureSection load='3wka' size='340' side='right' caption='[[3wka]], [[Resolution\|resolution]] 2.01Å' scene=''>		<StructureSection load='3wka' size='340' side='right' caption='[[3wka]], [[Resolution\|resolution]] 2.01Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3wk4\|3wk4]], [[3wk5\|3wk5]], [[3wk6\|3wk6]], [[3wk7\|3wk7]], [[3wk8\|3wk8]], [[3wk9\|3wk9]], [[3wkb\|3wkb]], [[3wkc\|3wkc]], [[3wkd\|3wkd]], [[3wke\|3wke]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3wk4\|3wk4]], [[3wk5\|3wk5]], [[3wk6\|3wk6]], [[3wk7\|3wk7]], [[3wk8\|3wk8]], [[3wk9\|3wk9]], [[3wkb\|3wkb]], [[3wkc\|3wkc]], [[3wkd\|3wkd]], [[3wke\|3wke]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EPHX2 ([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">EPHX2 ([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=3wka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wka OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wka RCSB], [http://www.ebi.ac.uk/pdbsum/3wka 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=3wka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wka OCA], [http://pdbe.org/3wka PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3wka RCSB], [http://www.ebi.ac.uk/pdbsum/3wka PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3wka 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 3wka" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Epoxide hydrolase\|Epoxide hydrolase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:28, 24 December 2014

OCA — Wed, 24 Dec 2014 07:28:36 GMT

←Older revision		Revision as of 07:28, 24 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3wka\| PDB=3wka \| SCENE= }}~~	+	==Crystal structure of soluble epoxide hydrolase in complex with fragment inhibitor==
-	===Crystal structure of soluble epoxide hydrolase in complex with fragment inhibitor===	+	<StructureSection load='3wka' size='340' side='right' caption='[[3wka]], [[Resolution\|resolution]] 2.01Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24656800}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[3wka]] is a 1 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=3WKA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WKA FirstGlance]. <br>
-	==Function==	+	</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=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=S0G:6-AMINO-1-METHYL-5-(PIPERIDIN-1-YL)PYRIMIDINE-2,4(1H,3H)-DIONE'>S0G</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3wk4\|3wk4]], [[3wk5\|3wk5]], [[3wk6\|3wk6]], [[3wk7\|3wk7]], [[3wk8\|3wk8]], [[3wk9\|3wk9]], [[3wkb\|3wkb]], [[3wkc\|3wkc]], [[3wkd\|3wkd]], [[3wke\|3wke]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EPHX2 ([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=3wka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wka OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wka RCSB], [http://www.ebi.ac.uk/pdbsum/3wka PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
	[[http://www.uniprot.org/uniprot/HYES_HUMAN HYES_HUMAN]] Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and p-nitrophenyl phospate.<ref>PMID:12574508</ref> <ref>PMID:12574510</ref>		[[http://www.uniprot.org/uniprot/HYES_HUMAN HYES_HUMAN]] Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and p-nitrophenyl phospate.<ref>PMID:12574508</ref> <ref>PMID:12574510</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Soluble epoxide hydrolase (sEH) is a component of the arachidonic acid cascade and is a candidate target for therapies for hypertension or inflammation. Although many sEH inhibitors are available, their scaffolds are not structurally diverse, and knowledge of their specific interactions with sEH is limited. To obtain detailed structural information about protein-ligand interactions, we conducted fragment screening of sEH, analyzed the fragments using high-throughput X-ray crystallography, and determined 126 fragment-bound structures at high resolution. Aminothiazole and benzimidazole derivatives were identified as novel scaffolds that bind to the catalytic triad of sEH with good ligand efficiency. We further identified fragment hits that bound to subpockets of sEH called the short and long branches. The water molecule conserved in the structure plays an important role in binding to the long branch, whereas Asp496 and the main chain of Phe497 form hydrogen bonds with fragment hits in the short branch. Fragment hits and their crystal structures provide structural insights into ligand binding to sEH that will facilitate the discovery of novel and potent inhibitors of sEH.

-	~~==About this Structure==~~	+	Structural insights into binding of inhibitors to soluble epoxide hydrolase gained by fragment screening and X-ray crystallography.,Amano Y, Yamaguchi T, Tanabe E Bioorg Med Chem. 2014 Apr 15;22(8):2427-34. doi: 10.1016/j.bmc.2014.03.001. Epub , 2014 Mar 12. PMID:24656800<ref>PMID:24656800</ref>
-	~~[[3wka]] is a 1 chain structure~~. ~~Full crystallographic information is available from [http~~:/~~/oca~~.~~weizmann~~.ac.~~il/oca-bin/ocashort?id=3WKA OCA]~~.	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:024656800</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
-	[[Category: Amano, Y.]]	+	== References ==
-	[[Category: Tanabe, E.]]	+	<references/>
-	[[Category: Yamaguchi, T.]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Amano, Y]]
		+	[[Category: Tanabe, E]]
		+	[[Category: Yamaguchi, T]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 09:37, 16 April 2014

OCA — Wed, 16 Apr 2014 09:37:14 GMT

←Older revision		Revision as of 09:37, 16 April 2014
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_3wka\| PDB=3wka \| SCENE= }}
		+	===Crystal structure of soluble epoxide hydrolase in complex with fragment inhibitor===
		+	{{ABSTRACT_PUBMED_24656800}}

-	The ~~entry 3wka is ON HOLD~~	+	==Function==
		+	[[http://www.uniprot.org/uniprot/HYES_HUMAN HYES_HUMAN]] Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and p-nitrophenyl phospate.<ref>PMID:12574508</ref> <ref>PMID:12574510</ref>

-	~~Authors~~: ~~Amano, Y~~.~~, Yamaguchi, T~~.~~, Tanabe, E~~.	+	==About this Structure==
		+	[[3wka]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WKA OCA].

-	~~Description~~: ~~Crystal structure of soluble epoxide~~ hydrolase ~~in complex with fragment~~ inhibitor	+	==Reference==
		+	<ref group="xtra">PMID:024656800</ref><references group="xtra"/><references/>
		+	[[Category: Amano, Y.]]
		+	[[Category: Tanabe, E.]]
		+	[[Category: Yamaguchi, T.]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]

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

OCA — Wed, 23 Oct 2013 05:34:38 GMT

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

←Older revision

Revision as of 05:34, 23 October 2013

OCA: New page: '''Unreleased structure''' The entry 3wka is ON HOLD Authors: Amano, Y., Yamaguchi, T., Tanabe, E. Description: Crystal structure of soluble epoxide hydrolase in complex with fragment ...

OCA — Wed, 23 Oct 2013 05:34:37 GMT

New page: '''Unreleased structure''' The entry 3wka is ON HOLD Authors: Amano, Y., Yamaguchi, T., Tanabe, E. Description: Crystal structure of soluble epoxide hydrolase in complex with fragment ...

New page

'''Unreleased structure'''

The entry 3wka is ON HOLD

Authors: Amano, Y., Yamaguchi, T., Tanabe, E.

Description: Crystal structure of soluble epoxide hydrolase in complex with fragment inhibitor