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==Crystal structure of human soluble epoxide hydrolase complexed with N-cycloheptyl-1-(mesitylsulfonyl)piperidine-4-carboxamide.== | ==Crystal structure of human soluble epoxide hydrolase complexed with N-cycloheptyl-1-(mesitylsulfonyl)piperidine-4-carboxamide.== | ||
<StructureSection load='4hai' size='340' side='right' caption='[[4hai]], [[Resolution|resolution]] 2.55Å' scene=''> | <StructureSection load='4hai' size='340' side='right'caption='[[4hai]], [[Resolution|resolution]] 2.55Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4hai]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4hai]] 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=4HAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HAI FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=I23:N-CYCLOHEPTYL-1-[(2,4,6-TRIMETHYLPHENYL)SULFONYL]PIPERIDINE-4-CARBOXAMIDE'>I23</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.55Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I23:N-CYCLOHEPTYL-1-[(2,4,6-TRIMETHYLPHENYL)SULFONYL]PIPERIDINE-4-CARBOXAMIDE'>I23</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4hai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hai OCA], [https://pdbe.org/4hai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hai RCSB], [https://www.ebi.ac.uk/pdbsum/4hai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hai ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 17: | Line 18: | ||
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 4hai" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Epoxide hydrolase 3D structures|Epoxide hydrolase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 22: | Line 27: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Deng | [[Category: Large Structures]] | ||
[[Category: Hammock | [[Category: Deng S]] | ||
[[Category: Morisseau | [[Category: Hammock BD]] | ||
[[Category: Newcomer | [[Category: Morisseau C]] | ||
[[Category: Pakhomova | [[Category: Newcomer ME]] | ||
[[Category: Pecic | [[Category: Pakhomova S]] | ||
[[Category: Zhu | [[Category: Pecic S]] | ||
[[Category: Zhu Z]] | |||
Latest revision as of 18:02, 20 September 2023
Crystal structure of human soluble epoxide hydrolase complexed with N-cycloheptyl-1-(mesitylsulfonyl)piperidine-4-carboxamide.Crystal structure of human soluble epoxide hydrolase complexed with N-cycloheptyl-1-(mesitylsulfonyl)piperidine-4-carboxamide.
Structural highlights
FunctionHYES_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 PubMedA series of potent amide non-urea inhibitors of soluble epoxide hydrolase (sEH) is disclosed. The inhibition of soluble epoxide hydrolase leads to elevated levels of epoxyeicosatrienoic acids (EETs), and thus inhibitors of sEH represent one of a novel approach to the development of vasodilatory and anti-inflammatory drugs. Structure-activities studies guided optimization of a lead compound, identified through high-throughput screening, gave rise to sub-nanomolar inhibitors of human sEH with stability in human liver microsomal assay suitable for preclinical development. Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors.,Pecic S, Pakhomova S, Newcomer ME, Morisseau C, Hammock BD, Zhu Z, Rinderspacher A, Deng SX Bioorg Med Chem Lett. 2013 Jan 15;23(2):417-21. doi: 10.1016/j.bmcl.2012.11.084. , Epub 2012 Dec 1. PMID:23237835[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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