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4y2s

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==Structure of soluble epoxide hydrolase in complex with 1-[3-(trifluoromethyl)phenyl]-1H-pyrazol-4-ol==
==Structure of soluble epoxide hydrolase in complex with 1-[3-(trifluoromethyl)phenyl]-1H-pyrazol-4-ol==
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<StructureSection load='4y2s' size='340' side='right' caption='[[4y2s]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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<StructureSection load='4y2s' size='340' side='right'caption='[[4y2s]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4y2s]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y2S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y2S FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4y2s]] 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=4Y2S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y2S FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=49P:1-[3-(TRIFLUOROMETHYL)PHENYL]-1H-PYRAZOL-4-OL'>49P</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4y2j|4y2j]], [[4y2p|4y2p]], [[4y2q|4y2q]], [[4y2r|4y2r]], [[4y2t|4y2t]], [[4y2u|4y2u]], [[4y2v|4y2v]], [[4y2x|4y2x]], [[4y2y|4y2y]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=49P:1-[3-(TRIFLUOROMETHYL)PHENYL]-1H-PYRAZOL-4-OL'>49P</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4y2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y2s OCA], [https://pdbe.org/4y2s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y2s RCSB], [https://www.ebi.ac.uk/pdbsum/4y2s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y2s ProSAT]</span></td></tr>
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<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=4y2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y2s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4y2s RCSB], [http://www.ebi.ac.uk/pdbsum/4y2s PDBsum]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[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>
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Soluble epoxide hydrolase (sEH) is a potential target for the treatment of inflammation and hypertension. X-ray crystallographic fragment screening was used to identify fragment hits and their binding modes. Eight fragment hits were identified via soaking of sEH crystals with fragment cocktails, and the co-crystal structures of these hits were determined via individual soaking. Based on the binding mode, N-ethylmethylamine was identified as a promising scaffold that forms hydrogen bonds with the catalytic residues of sEH, Asp335, Tyr383, and Tyr466. Compounds containing this scaffold were selected from an in-house chemical library and assayed. Although the starting fragment had a weak inhibitory activity (IC50: 800muM), we identified potent inhibitors including 2-({[2-(adamantan-1-yl)ethyl]amino}methyl)phenol exhibiting the highest inhibitory activity (IC50: 0.51muM). This corresponded to a more than 1500-fold increase in inhibitory activity compared to the starting fragment. Co-crystal structures of the hit compounds demonstrate that the binding of N-ethylmethylamine to catalytic residues is similar to that of the starting fragment. We therefore consider crystallographic fragment screening to be appropriate for the identification of weak but promising fragment hits.
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Identification of N-ethylmethylamine as a novel scaffold for inhibitors of soluble epoxide hydrolase by crystallographic fragment screening.,Amano Y, Tanabe E, Yamaguchi T Bioorg Med Chem. 2015 May 15;23(10):2310-7. doi: 10.1016/j.bmc.2015.03.083. Epub , 2015 Apr 6. PMID:25862210<ref>PMID:25862210</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
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</div>
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*[[Epoxide hydrolase 3D structures|Epoxide hydrolase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Soluble epoxide hydrolase]]
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[[Category: Homo sapiens]]
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[[Category: Amano, Y]]
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[[Category: Large Structures]]
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[[Category: Yamaguchi, T]]
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[[Category: Amano Y]]
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[[Category: Hydrolase]]
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[[Category: Yamaguchi T]]
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[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
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Current revision

Structure of soluble epoxide hydrolase in complex with 1-[3-(trifluoromethyl)phenyl]-1H-pyrazol-4-ol

PDB ID 4y2s

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