4j03
Crystal 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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