3i1y

<StructureSection load='3i1y' size='340' side='right' caption='[[3i1y]], [[Resolution|resolution]] 2.47&Aring;' scene=''>

<table><tr><td colspan='2'>[[3i1y]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I1Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3I1Y FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=33N:N-(3,3-DIPHENYLPROPYL)PYRIDINE-3-CARBOXAMIDE'>33N</scene></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=3i1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i1y OCA], [http://pdbe.org/3i1y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3i1y RCSB], [http://www.ebi.ac.uk/pdbsum/3i1y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3i1y ProSAT]</span></td></tr>

== 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>

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== Publication Abstract from PubMed ==

Inhibition of soluble epoxide hydrolase (sEH) is hypothesized to lead to an increase in circulating levels of epoxyeicosatrienoic acids, resulting in the potentiation of their in vivo pharmacological properties. As part of an effort to identify inhibitors of sEH with high and sustained plasma exposure, we recently performed a high throughput screen of our compound collection. The screen identified N-(3,3-diphenyl-propyl)-nicotinamide as a potent inhibitor of sEH. Further profiling of this lead revealed short metabolic half-lives in microsomes and rapid clearance in the rat. Consistent with these observations, the determination of the in vitro metabolic profile of N-(3,3-diphenyl-propyl)-nicotinamide in rat liver microsomes revealed extensive oxidative metabolism and a propensity for metabolite switching. Lead optimization, guided by the analysis of the solid-state costructure of N-(3,3-diphenyl-propyl)-nicotinamide bound to human sEH, led to the identification of a class of potent and selective inhibitors. An inhibitor from this class displayed an attractive in vitro metabolic profile and high and sustained plasma exposure in the rat after oral administration.

Structure-based optimization of arylamides as inhibitors of soluble epoxide hydrolase.,Eldrup AB, Soleymanzadeh F, Taylor SJ, Muegge I, Farrow NA, Joseph D, McKellop K, Man CC, Kukulka A, De Lombaert S J Med Chem. 2009 Oct 8;52(19):5880-95. PMID:19746975<ref>PMID:19746975</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 3i1y" style="background-color:#fffaf0;"></div>

*[[Epoxide hydrolase|Epoxide hydrolase]]

[[Category: Human]]

[[Category: Soluble epoxide hydrolase]]

[[Category: Farrow, N A]]

[[Category: Polymorphism]]