4x6y: Difference between revisions
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==Human soluble epoxide hydrolase in complex with a cyclopropyl urea derivative== | ==Human soluble epoxide hydrolase in complex with a cyclopropyl urea derivative== | ||
<StructureSection load='4x6y' size='340' side='right' caption='[[4x6y]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='4x6y' size='340' side='right' caption='[[4x6y]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4x6x|4x6x]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4x6x|4x6x]]</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=4x6y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x6y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4x6y RCSB], [http://www.ebi.ac.uk/pdbsum/4x6y 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=4x6y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x6y OCA], [http://pdbe.org/4x6y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x6y RCSB], [http://www.ebi.ac.uk/pdbsum/4x6y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x6y ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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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 4x6y" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Epoxide hydrolase|Epoxide hydrolase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 03:16, 26 January 2017
Human soluble epoxide hydrolase in complex with a cyclopropyl urea derivativeHuman soluble epoxide hydrolase in complex with a cyclopropyl urea derivative
Structural highlights
Function[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.[1] [2] Publication Abstract from PubMedWe 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). 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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