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==Crystal Structure of soluble epoxide Hydrolase==
==Crystal Structure of soluble epoxide Hydrolase==
<StructureSection load='3koo' size='340' side='right' caption='[[3koo]], [[Resolution|resolution]] 2.79&Aring;' scene=''>
<StructureSection load='3koo' size='340' side='right'caption='[[3koo]], [[Resolution|resolution]] 2.79&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3koo]] 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=3KOO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KOO FirstGlance]. <br>
<table><tr><td colspan='2'>[[3koo]] 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=3KOO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KOO FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=24D:N-(2,4-DICHLOROBENZYL)-4-(PYRIMIDIN-2-YLOXY)PIPERIDINE-1-CARBOXAMIDE'>24D</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]] 2.791&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=24D:N-(2,4-DICHLOROBENZYL)-4-(PYRIMIDIN-2-YLOXY)PIPERIDINE-1-CARBOXAMIDE'>24D</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=3koo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3koo OCA], [https://pdbe.org/3koo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3koo RCSB], [https://www.ebi.ac.uk/pdbsum/3koo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3koo 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=3koo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3koo OCA], [http://pdbe.org/3koo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3koo RCSB], [http://www.ebi.ac.uk/pdbsum/3koo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3koo 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>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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=3koo 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=3koo ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Inhibition of sEH is hypothesized to lead to an increase in epoxyeicosatrienoic acids resulting in the potentiation of their anti-inflammatory and vasodilatory effects. In an effort to explore sEH inhibition as an avenue for the development of vasodilatory and cardio- or renal-protective agents, a lead identified through high-throughput screening was optimized, guided by the determination of a solid state co-structure with sEH. Replacement of potential toxicophores was followed by optimization of cell-based potency and ADME properties to provide a new class of functionally potent sEH inhibitors with attractive in vitro metabolic profiles and high and sustained plasma exposures after oral administration in the rat.
Optimization of piperidyl-ureas as inhibitors of soluble epoxide hydrolase.,Eldrup AB, Soleymanzadeh F, Farrow NA, Kukulka A, De Lombaert S Bioorg Med Chem Lett. 2010 Jan 15;20(2):571-5. Epub 2009 Nov 22. PMID:19969453<ref>PMID:19969453</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3koo" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Epoxide hydrolase|Epoxide hydrolase]]
*[[Epoxide hydrolase 3D structures|Epoxide hydrolase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Soluble epoxide hydrolase]]
[[Category: Large Structures]]
[[Category: Farrow, N A]]
[[Category: Farrow NA]]
[[Category: Hydrolase]]
Retrieved from "https://proteopedia.org/3koo"