4j03: Difference between revisions
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==Crystal structure of human soluble epoxide hydrolase complexed with fulvestrant== | ==Crystal structure of human soluble epoxide hydrolase complexed with fulvestrant== | ||
<StructureSection load='4j03' size='340' side='right' caption='[[4j03]], [[Resolution|resolution]] 2.92Å' scene=''> | <StructureSection load='4j03' size='340' side='right'caption='[[4j03]], [[Resolution|resolution]] 2.92Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4j03]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4j03]] 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=4J03 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J03 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FVS:(7BETA,9BETA,13ALPHA,17BETA)-7-{9-[(R)-(4,4,5,5,5-PENTAFLUOROPENTYL)SULFINYL]NONYL}ESTRA-1(10),2,4-TRIENE-3,17-DIOL'>FVS</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]] 2.92Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FVS:(7BETA,9BETA,13ALPHA,17BETA)-7-{9-[(R)-(4,4,5,5,5-PENTAFLUOROPENTYL)SULFINYL]NONYL}ESTRA-1(10),2,4-TRIENE-3,17-DIOL'>FVS</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=4j03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j03 OCA], [https://pdbe.org/4j03 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j03 RCSB], [https://www.ebi.ac.uk/pdbsum/4j03 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j03 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== 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 == | ||
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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 4j03" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Epoxide hydrolase 3D structures|Epoxide hydrolase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 20: | Line 27: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Hammock | [[Category: Large Structures]] | ||
[[Category: Hwang | [[Category: Hammock BD]] | ||
[[Category: Morisseau | [[Category: Hwang SH]] | ||
[[Category: Newcomer | [[Category: Morisseau C]] | ||
[[Category: Pakhomova | [[Category: Newcomer ME]] | ||
[[Category: Pakhomova S]] | |||
Latest revision as of 18:34, 20 September 2023
Crystal structure of human soluble epoxide hydrolase complexed with fulvestrantCrystal structure of human soluble epoxide hydrolase complexed with fulvestrant
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 PubMedThe soluble epoxide hydrolase (sEH) is a key enzyme in the metabolism of epoxy-fatty acids, signaling molecules involved in numerous biologies. Toward finding novel inhibitors of sEH, a library of known drugs was tested for inhibition of sEH. We found that fulvestrant, an anticancer agent, is a potent (KI=26nM) competitive inhibitor of sEH. From this observation, we found that alkyl-sulfoxides represent a new kind of pharmacophore for the inhibition of sEH. Inhibition of soluble epoxide hydrolase by fulvestrant and sulfoxides.,Morisseau C, Pakhomova S, Hwang SH, Newcomer ME, Hammock BD Bioorg Med Chem Lett. 2013 Jul 1;23(13):3818-21. doi: 10.1016/j.bmcl.2013.04.083., Epub 2013 May 6. PMID:23684894[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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