6hgx: Difference between revisions
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The | ==Soluble epoxide hydrolase in complex with 1-(4-((4-(tert-butyl)morpholin-2-yl)methoxy)phenyl)-3-cyclohexylurea== | ||
<StructureSection load='6hgx' size='340' side='right'caption='[[6hgx]], [[Resolution|resolution]] 2.16Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6hgx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HGX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HGX FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=G3T:1-[4-[[(2~{S})-4-~{tert}-butylmorpholin-2-yl]methoxy]phenyl]-3-cyclohexyl-urea'>G3T</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6hgv|6hgv]]</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=6hgx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hgx OCA], [http://pdbe.org/6hgx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hgx RCSB], [http://www.ebi.ac.uk/pdbsum/6hgx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hgx ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Selective optimization of side activities is a valuable source of novel lead structures in drug discovery. In this study, a computer-aided approach was used to deorphanize the pleiotropic cholesterol-lowering effects of the beta-blocker talinolol, which result from the inhibition of the enzyme soluble epoxide hydrolase (sEH). X-ray structure analysis of the sEH in complex with talinolol enables a straightforward optimization of inhibitory potency. The resulting lead structure exhibited in vivo activity in a rat model of diabetic neuropatic pain. | |||
Computer-Aided Selective Optimization of Side Activities of Talinolol.,Hiesinger K, Kramer JS, Achenbach J, Moser D, Weber J, Wittmann SK, Morisseau C, Angioni C, Geisslinger G, Kahnt AS, Kaiser A, Proschak A, Steinhilber D, Pogoryelov D, Wagner K, Hammock BD, Proschak E ACS Med Chem Lett. 2019 May 29;10(6):899-903. doi:, 10.1021/acsmedchemlett.9b00075. eCollection 2019 Jun 13. PMID:31223445<ref>PMID:31223445</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6hgx" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Hiesinger, K]] | [[Category: Hiesinger, K]] | ||
[[Category: Kramer, J S]] | |||
[[Category: Pogoryelov, D]] | [[Category: Pogoryelov, D]] | ||
[[Category: | [[Category: Proschak, E]] | ||
[[Category: Complex]] | |||
[[Category: Hydrolase]] | |||
[[Category: Inhibitor]] | |||
[[Category: Seh]] | |||