3otq

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Soluble Epoxide Hydrolase in complex with pyrazole antagonistSoluble Epoxide Hydrolase in complex with pyrazole antagonist

Structural highlights

3otq is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:EPHX2 (HUMAN)
Activity:Soluble epoxide hydrolase, with EC number 3.3.2.10
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.[1] [2]

Publication Abstract from PubMed

A novel series of pyrazole sEH inhibitors is reported. Lead optimization efforts to replace the aniline core are also described. In particular, 2-pyridine, 3-pyridine and pyridazine analogs are potent sEH inhibitors with favorable CYP3A4 inhibitory and microsomal stability profiles.

Substituted pyrazoles as novel sEH antagonist: investigation of key binding interactions within the catalytic domain.,Lo HY, Man CC, Fleck RW, Farrow NA, Ingraham RH, Kukulka A, Proudfoot JR, Betageri R, Kirrane T, Patel U, Sharma R, Hoermann MA, Kabcenell A, Lombaert SD Bioorg Med Chem Lett. 2010 Nov 15;20(22):6379-83. Epub 2010 Sep 19. PMID:20934334[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Cronin A, Mowbray S, Durk H, Homburg S, Fleming I, Fisslthaler B, Oesch F, Arand M. The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1552-7. Epub 2003 Feb 6. PMID:12574508 doi:10.1073/pnas.0437829100
  2. ↑ Newman JW, Morisseau C, Harris TR, Hammock BD. The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1558-63. Epub 2003 Feb 6. PMID:12574510 doi:10.1073/pnas.0437724100
  3. ↑ Lo HY, Man CC, Fleck RW, Farrow NA, Ingraham RH, Kukulka A, Proudfoot JR, Betageri R, Kirrane T, Patel U, Sharma R, Hoermann MA, Kabcenell A, Lombaert SD. Substituted pyrazoles as novel sEH antagonist: investigation of key binding interactions within the catalytic domain. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6379-83. Epub 2010 Sep 19. PMID:20934334 doi:10.1016/j.bmcl.2010.09.095

3otq, resolution 3.00Å

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