4x6x

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'''Unreleased structure'''
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==Human soluble epoxide hydrolase in complex with a three substituted cyclopropane derivative==
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<StructureSection load='4x6x' size='340' side='right' caption='[[4x6x]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4x6x]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X6X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X6X 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=S74:3-{4-[(1-{[(1S,2R,3S)-2,3-DIPHENYLCYCLOPROPYL]CARBAMOYL}PIPERIDIN-4-YL)OXY]PHENYL}PROPANOIC+ACID'>S74</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4x6y|4x6y]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4x6x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x6x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4x6x RCSB], [http://www.ebi.ac.uk/pdbsum/4x6x PDBsum]</span></td></tr>
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</table>
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== 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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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We have previously reported a series of cyclopropyl urea derivatives as potent orally available soluble epoxide hydrolase (sEH) inhibitors. Here, we designed and synthesized three substituted cyclopropane derivatives that occupy all available pockets of sEH catalytic domain. Compound 14 with a diphenyl substituted cyclopropyl moiety showed good sEH inhibitory activity. Co-crystal structure of this compound and human sEH hydrolase catalytic domain revealed enzyme pockets occupied by the phenoxypiperidine part and the diphenyl cyclopropyl moiety. Furthermore, investigation of the phenoxypiperidine part of compound 14 resulted in the discovery of compound 19, which showed potent sEH inhibitory activity (sub-nM sEH IC50 values).
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The entry 4x6x is ON HOLD until Paper Publication
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Three-dimensional rational approach to the discovery of potent substituted cyclopropyl urea soluble epoxide hydrolase inhibitors.,Takai K, Chiyo N, Nakajima T, Nariai T, Ishikawa C, Nakatani S, Ikeno A, Yamamoto S, Sone T Bioorg Med Chem Lett. 2015 Apr 15;25(8):1705-8. doi: 10.1016/j.bmcl.2015.02.076. , Epub 2015 Mar 7. PMID:25800114<ref>PMID:25800114</ref>
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Authors: Chiyo, N., Takai, K., Ishii, T.
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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Description: Human soluble epoxide hydrolase in complex with a three substituted cyclopropane derivative
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== References ==
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[[Category: Unreleased Structures]]
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Soluble epoxide hydrolase]]
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[[Category: Chiyo, N]]
[[Category: Ishii, T]]
[[Category: Ishii, T]]
[[Category: Takai, K]]
[[Category: Takai, K]]
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[[Category: Chiyo, N]]
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[[Category: Hydrolase]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]

Revision as of 11:07, 8 April 2015

Human soluble epoxide hydrolase in complex with a three substituted cyclopropane derivative

4x6x, resolution 1.80Å

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