3i1y - Revision history

OCA at 10:02, 21 February 2024

OCA — Wed, 21 Feb 2024 10:02:55 GMT

←Older revision		Revision as of 10:02, 21 February 2024
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	==Crystal Structure of soluble epoxide Hydrolase==		==Crystal Structure of soluble epoxide Hydrolase==
-	<StructureSection load='3i1y' size='340' side='right'caption='[[3i1y]]' scene=''>	+	<StructureSection load='3i1y' size='340' side='right'caption='[[3i1y]], [[Resolution\|resolution]] 2.47Å' 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=3I1Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I1Y FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3i1y]] 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=3I1Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I1Y 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=3i1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i1y OCA], [https://pdbe.org/3i1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i1y RCSB], [https://www.ebi.ac.uk/pdbsum/3i1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i1y 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]] 2.469Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=33N:N-(3,3-DIPHENYLPROPYL)PYRIDINE-3-CARBOXAMIDE'>33N</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=3i1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i1y OCA], [https://pdbe.org/3i1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i1y RCSB], [https://www.ebi.ac.uk/pdbsum/3i1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i1y 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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 19:		Line 23:
	==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: Farrow NA]]		[[Category: Farrow NA]]

OCA at 11:20, 6 April 2022

OCA — Wed, 06 Apr 2022 11:20:19 GMT

←Older revision		Revision as of 11:20, 6 April 2022
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	==Crystal Structure of soluble epoxide Hydrolase==		==Crystal Structure of soluble epoxide Hydrolase==
-	<StructureSection load='3i1y' size='340' side='right' caption='[[3i1y]]~~, [[Resolution\|resolution]] 2.47Å~~' scene=''>	+	<StructureSection load='3i1y' size='340' side='right'caption='[[3i1y]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>~~[[3i1y]] 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=3I1Y OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3I1Y FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I1Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I1Y FirstGlance]. <br>
-	</td></tr>~~<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=33N:N-(3,3-DIPHENYLPROPYL)PYRIDINE-3-CARBOXAMIDE'>33N</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=3i1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i1y OCA], [https://pdbe.org/3i1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i1y RCSB], [https://www.ebi.ac.uk/pdbsum/3i1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i1y ProSAT]</span></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3i28\|3i28]]</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Soluble_epoxide_hydrolase Soluble epoxide hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.10 3.3.2.10] </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=3i1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i1y OCA], [~~http~~://pdbe.org/3i1y PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3i1y RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3i1y PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3i1y ProSAT]</span></td></tr>	+
	</table>		</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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 22:		Line 16:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3i1y ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3i1y ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Inhibition of soluble epoxide hydrolase (sEH) is hypothesized to lead to an increase in circulating levels of epoxyeicosatrienoic acids, resulting in the potentiation of their in vivo pharmacological properties. As part of an effort to identify inhibitors of sEH with high and sustained plasma exposure, we recently performed a high throughput screen of our compound collection. The screen identified N-(3,3-diphenyl-propyl)-nicotinamide as a potent inhibitor of sEH. Further profiling of this lead revealed short metabolic half-lives in microsomes and rapid clearance in the rat. Consistent with these observations, the determination of the in vitro metabolic profile of N-(3,3-diphenyl-propyl)-nicotinamide in rat liver microsomes revealed extensive oxidative metabolism and a propensity for metabolite switching. Lead optimization, guided by the analysis of the solid-state costructure of N-(3,3-diphenyl-propyl)-nicotinamide bound to human sEH, led to the identification of a class of potent and selective inhibitors. An inhibitor from this class displayed an attractive in vitro metabolic profile and high and sustained plasma exposure in the rat after oral administration.
-
-	Structure-based optimization of arylamides as inhibitors of soluble epoxide hydrolase.,Eldrup AB, Soleymanzadeh F, Taylor SJ, Muegge I, Farrow NA, Joseph D, McKellop K, Man CC, Kukulka A, De Lombaert S J Med Chem. 2009 Oct 8;52(19):5880-95. PMID:19746975<ref>PMID:19746975</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 3i1y" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
-	*[[Epoxide hydrolase\|Epoxide hydrolase]]	+	*[[Epoxide hydrolase 3D structures\|Epoxide hydrolase 3D structures]]
-	~~== References ==~~	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human]]~~	+	[[Category: Large Structures]]
-	~~[[Category: Soluble epoxide hydrolase~~]]	+	[[Category: Farrow NA]]
-	[[Category: Farrow~~, N A]]~~	+
-	~~[[Category: Aromatic hydrocarbons catabolism]]~~	+
-	~~[[Category: Cytoplasm]]~~	+
-	~~[[Category: Detoxification]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Magnesium]]~~	+
-	~~[[Category: Metal-binding]]~~	+
-	~~[[Category: Peroxisome]]~~	+
-	~~[[Category: Polymorphism~~]]	+

OCA at 09:21, 19 December 2018

OCA — Wed, 19 Dec 2018 09:21:14 GMT

←Older revision		Revision as of 09:21, 19 December 2018
Line 1:		Line 1:
		+
	==Crystal Structure of soluble epoxide Hydrolase==		==Crystal Structure of soluble epoxide Hydrolase==
	<StructureSection load='3i1y' size='340' side='right' caption='[[3i1y]], [[Resolution\|resolution]] 2.47Å' scene=''>		<StructureSection load='3i1y' size='340' side='right' caption='[[3i1y]], [[Resolution\|resolution]] 2.47Å' scene=''>
Line 7:		Line 8:
	<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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Soluble_epoxide_hydrolase Soluble epoxide hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.10 3.3.2.10] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Soluble_epoxide_hydrolase Soluble epoxide hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.10 3.3.2.10] </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=3i1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i1y OCA], [http://pdbe.org/3i1y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3i1y RCSB], [http://www.ebi.ac.uk/pdbsum/3i1y 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=3i1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i1y OCA], [http://pdbe.org/3i1y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3i1y RCSB], [http://www.ebi.ac.uk/pdbsum/3i1y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3i1y ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 15:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i1/3i1y_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i1/3i1y_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 41:		Line 42:
	[[Category: Farrow, N A]]		[[Category: Farrow, N A]]
	[[Category: Aromatic hydrocarbons catabolism]]		[[Category: Aromatic hydrocarbons catabolism]]
		+	[[Category: Cytoplasm]]
	[[Category: Detoxification]]		[[Category: Detoxification]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
Line 46:		Line 48:
	[[Category: Metal-binding]]		[[Category: Metal-binding]]
	[[Category: Peroxisome]]		[[Category: Peroxisome]]
		+	[[Category: Polymorphism]]

OCA at 19:29, 8 February 2016

OCA — Mon, 08 Feb 2016 19:29:33 GMT

←Older revision		Revision as of 19:29, 8 February 2016
Line 2:		Line 2:
	<StructureSection load='3i1y' size='340' side='right' caption='[[3i1y]], [[Resolution\|resolution]] 2.47Å' scene=''>		<StructureSection load='3i1y' size='340' side='right' caption='[[3i1y]], [[Resolution\|resolution]] 2.47Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3i1y]] is a 1 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=3I1Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3I1Y FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3i1y]] 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=3I1Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3I1Y FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=33N:N-(3,3-DIPHENYLPROPYL)PYRIDINE-3-CARBOXAMIDE'>33N</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=33N:N-(3,3-DIPHENYLPROPYL)PYRIDINE-3-CARBOXAMIDE'>33N</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3i28\|3i28]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3i28\|3i28]]</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 ~~Homo sapiens~~])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Soluble_epoxide_hydrolase Soluble epoxide hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.10 3.3.2.10] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Soluble_epoxide_hydrolase Soluble epoxide hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.10 3.3.2.10] </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=3i1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i1y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3i1y RCSB], [http://www.ebi.ac.uk/pdbsum/3i1y 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=3i1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i1y OCA], [http://pdbe.org/3i1y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3i1y RCSB], [http://www.ebi.ac.uk/pdbsum/3i1y PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 19:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3i1y ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 29:		Line 29:
	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 3i1y" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Epoxide hydrolase\|Epoxide hydrolase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Soluble epoxide hydrolase]]		[[Category: Soluble epoxide hydrolase]]
	[[Category: Farrow, N A]]		[[Category: Farrow, N A]]

OCA at 01:39, 25 December 2014

OCA — Thu, 25 Dec 2014 01:39:07 GMT

←Older revision		Revision as of 01:39, 25 December 2014
Line 9:		Line 9:
	<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=3i1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i1y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3i1y RCSB], [http://www.ebi.ac.uk/pdbsum/3i1y 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=3i1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i1y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3i1y RCSB], [http://www.ebi.ac.uk/pdbsum/3i1y PDBsum]</span></td></tr>
	</table>		</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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 06:07, 18 December 2014

OCA — Thu, 18 Dec 2014 06:07:15 GMT

←Older revision		Revision as of 06:07, 18 December 2014
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-	~~{{STRUCTURE_3i1y~~\| ~~PDB~~=3i1y \| ~~SCENE~~= }}	+	==Crystal Structure of soluble epoxide Hydrolase==
-	===~~Crystal Structure of soluble~~ epoxide ~~Hydrolase~~===	+	<StructureSection load='3i1y' size='340' side='right' caption='[[3i1y]], [[Resolution\|resolution]] 2.47Å' scene=''>
-	~~{{ABSTRACT_PUBMED_19746975}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3i1y]] is a 1 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=3I1Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3I1Y FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=33N:N-(3,3-DIPHENYLPROPYL)PYRIDINE-3-CARBOXAMIDE'>33N</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3i28\|3i28]]</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 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Soluble_epoxide_hydrolase Soluble epoxide hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.10 3.3.2.10] </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=3i1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i1y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3i1y RCSB], [http://www.ebi.ac.uk/pdbsum/3i1y PDBsum]</span></td></tr>
		+	</table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i1/3i1y_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Inhibition of soluble epoxide hydrolase (sEH) is hypothesized to lead to an increase in circulating levels of epoxyeicosatrienoic acids, resulting in the potentiation of their in vivo pharmacological properties. As part of an effort to identify inhibitors of sEH with high and sustained plasma exposure, we recently performed a high throughput screen of our compound collection. The screen identified N-(3,3-diphenyl-propyl)-nicotinamide as a potent inhibitor of sEH. Further profiling of this lead revealed short metabolic half-lives in microsomes and rapid clearance in the rat. Consistent with these observations, the determination of the in vitro metabolic profile of N-(3,3-diphenyl-propyl)-nicotinamide in rat liver microsomes revealed extensive oxidative metabolism and a propensity for metabolite switching. Lead optimization, guided by the analysis of the solid-state costructure of N-(3,3-diphenyl-propyl)-nicotinamide bound to human sEH, led to the identification of a class of potent and selective inhibitors. An inhibitor from this class displayed an attractive in vitro metabolic profile and high and sustained plasma exposure in the rat after oral administration.

-	~~==About this~~ Structure==	+	Structure-based optimization of arylamides as inhibitors of soluble epoxide hydrolase.,Eldrup AB, Soleymanzadeh F, Taylor SJ, Muegge I, Farrow NA, Joseph D, McKellop K, Man CC, Kukulka A, De Lombaert S J Med Chem. 2009 Oct 8;52(19):5880-95. PMID:19746975<ref>PMID:19746975</ref>
-	~~[[3i1y]] is a 1 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=3I1Y OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	<~~ref group="xtra">PMID:019746975<~~/~~ref~~><~~references group="xtra"~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Soluble epoxide hydrolase]]		[[Category: Soluble epoxide hydrolase]]
-	[[Category: Farrow, N A.]]	+	[[Category: Farrow, N A]]
	[[Category: Aromatic hydrocarbons catabolism]]		[[Category: Aromatic hydrocarbons catabolism]]
	[[Category: Detoxification]]		[[Category: Detoxification]]

OCA: Protected "3i1y" [edit=sysop:move=sysop]

OCA — Wed, 13 Mar 2013 10:43:03 GMT

Protected "3i1y" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:43, 13 March 2013

OCA at 10:42, 13 March 2013

OCA — Wed, 13 Mar 2013 10:42:59 GMT

←Older revision		Revision as of 10:42, 13 March 2013
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-	{{Seed}}
-	[[Image:3i1y.png\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_3i1y", 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_3i1y\| PDB=3i1y \| SCENE= }}		{{STRUCTURE_3i1y\| PDB=3i1y \| SCENE= }}
-
	===Crystal Structure of soluble epoxide Hydrolase===		===Crystal Structure of soluble epoxide Hydrolase===
-
-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_19746975}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 19746975 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_19746975}}		{{ABSTRACT_PUBMED_19746975}}
-
-	==Disease==
-	Known disease associated with this structure: Hypercholesterolemia, familial, due to LDLR defect, modifier of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=132811 132811]]

	==About this Structure==		==About this Structure==
-	~~3I1Y~~ is a 1 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=3I1Y OCA].	+	[[3i1y]] is a 1 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=3I1Y OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~19746975~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019746975</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Soluble epoxide hydrolase]]		[[Category: Soluble epoxide hydrolase]]
	[[Category: Farrow, N A.]]		[[Category: Farrow, N A.]]
	[[Category: Aromatic hydrocarbons catabolism]]		[[Category: Aromatic hydrocarbons catabolism]]
-	[[Category: Cytoplasm]]
	[[Category: Detoxification]]		[[Category: Detoxification]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
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	[[Category: Metal-binding]]		[[Category: Metal-binding]]
	[[Category: Peroxisome]]		[[Category: Peroxisome]]
-	[[Category: Polymorphism]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jan 28 14:32:41 2010''

OCA at 12:32, 28 January 2010

OCA — Thu, 28 Jan 2010 12:32:41 GMT

←Older revision		Revision as of 12:32, 28 January 2010
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	{{Seed}}		{{Seed}}
-	[[Image:3i1y.~~jpg~~\|left\|200px]]	+	[[Image:3i1y.png\|left\|200px]]

	<!--		<!--
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	==About this Structure==		==About this Structure==
-	3I1Y is a 1 chain structure of 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=3I1Y OCA].	+	3I1Y is a 1 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=3I1Y OCA].

	==Reference==		==Reference==
Line 39:		Line 39:
	[[Category: Polymorphism]]		[[Category: Polymorphism]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed Oct~~ 14 10:20:~~23 2009~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jan 28 14:32:41 2010''

OCA at 08:20, 14 October 2009

OCA — Wed, 14 Oct 2009 08:20:24 GMT

←Older revision		Revision as of 08:20, 14 October 2009
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-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:3i1y.jpg\|left\|200px]]

-	The ~~entry 3i1y~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3i1y", 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_3i1y\| PDB=3i1y \| SCENE= }}

-	~~Authors: Farrow, N.A.~~	+	===Crystal Structure of soluble epoxide Hydrolase===

-	Description: Crystal Structure of soluble epoxide Hydrolase

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Jul 8 09~~:16:08 2009''	+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_19746975}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 19746975 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_19746975}}
		+
		+	==Disease==
		+	Known disease associated with this structure: Hypercholesterolemia, familial, due to LDLR defect, modifier of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=132811 132811]]
		+
		+	==About this Structure==
		+	3I1Y is a 1 chain structure of 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=3I1Y OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:19746975</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Soluble epoxide hydrolase]]
		+	[[Category: Farrow, N A.]]
		+	[[Category: Aromatic hydrocarbons catabolism]]
		+	[[Category: Cytoplasm]]
		+	[[Category: Detoxification]]
		+	[[Category: Hydrolase]]
		+	[[Category: Magnesium]]
		+	[[Category: Metal-binding]]
		+	[[Category: Peroxisome]]
		+	[[Category: Polymorphism]]
		+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 14 10:20:23 2009''