7a7g

Soluble epoxide hydrolase in complex with TK90

spinqualitylabelsall models 7a7g, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7a7g is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: TK9 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. Publication Abstract from PubMed The metabolic syndrome (MetS) is a constellation of cardiovascular and metabolic symptoms involving insulin resistance, steatohepatitis, obesity, hypertension, and heart disease, and patients suffering from MetS often require polypharmaceutical treatment. PPARgamma agonists are highly effective oral antidiabetics with great potential in MetS, which promote adipocyte browning and insulin sensitization. However, the application of PPARgamma agonists in clinics is restricted by potential cardiovascular adverse events. We have previously demonstrated that the racemic dual sEH/PPARgamma modulator RB394 (3) simultaneously improves all risk factors of MetS in vivo. In this study, we identify and characterize the eutomer of 3. We provide structural rationale for molecular recognition of the eutomer. Furthermore, we could show that the dual sEH/PPARgamma modulator is able to promote adipocyte browning and simultaneously exhibits cardioprotective activity which underlines its exciting potential in treatment of MetS. Combined Cardioprotective and Adipocyte Browning Effects Promoted by the Eutomer of Dual sEH/PPARgamma Modulator.,Hartmann M, Bibli SI, Tews D, Ni X, Kircher T, Kramer JS, Kilu W, Heering J, Hernandez-Olmos V, Weizel L, Scriba GKE, Krait S, Knapp S, Chaikuad A, Merk D, Fleming I, Fischer-Posovszky P, Proschak E J Med Chem. 2021 Mar 11;64(5):2815-2828. doi: 10.1021/acs.jmedchem.0c02063. Epub , 2021 Feb 23. PMID:33620196 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Epoxide hydrolase 3D structures

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