Function
Epoxide hydrolase (EH) converts epoxides to trans-dihydrodiols which are excreted from the body. Thus, EH acts as a detoxification agent. Epoxides are formed from degradation of aromatic compounds[1].
Bifunctional EH 2 or soluble EH (SEH) is a bifunctional enzyme with the C-terminal domain having EH activity and the N-terminal domain having lipid phosphatase activity.
Limonene-1,2-epoxide hydrolase catalyzes the conversion of limonene-1,2-epoxide to limonene-1,2-diol[2] . For details see limonene-1,2-epoxide hydrolase.
Disease
Inhibitors of Mycobacterium tuberculosis EH such as urea derivatives, are used as anti-tuberculosis drugs. The valpromide inhibitor of EH is used as anti-epileptic drug. Soluble EH plays a role in several diseases including cardiovascular ones and is a drug target for their therapy [3].
Relevance
Structural highlights
Biological assembly of Human soluble epoxide hydrolase is dimer.
Inhibitor binding site (PDB code 5alf).[4]
3D Structures of epoxide hydrolase
Epoxide hydrolase 3D structures
- ↑ Biswal BK, Morisseau C, Garen G, Cherney MM, Garen C, Niu C, Hammock BD, James MN. The molecular structure of epoxide hydrolase B from Mycobacterium tuberculosis and its complex with a urea-based inhibitor. J Mol Biol. 2008 Sep 12;381(4):897-912. Epub 2008 Jun 17. PMID:18585390 doi:10.1016/j.jmb.2008.06.030
- ↑ Arand M, Hallberg BM, Zou J, Bergfors T, Oesch F, van der Werf MJ, de Bont JA, Jones TA, Mowbray SL. Structure of Rhodococcus erythropolis limonene-1,2-epoxide hydrolase reveals a novel active site. EMBO J. 2003 Jun 2;22(11):2583-92. PMID:12773375 doi:https://dx.doi.org/10.1093/emboj/cdg275
- ↑ Imig JD, Hammock BD. Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases. Nat Rev Drug Discov. 2009 Oct;8(10):794-805. doi: 10.1038/nrd2875. PMID:19794443 doi:https://dx.doi.org/10.1038/nrd2875
- ↑ Oster L, Tapani S, Xue Y, Kack H. Successful generation of structural information for fragment-based drug discovery. Drug Discov Today. 2015 Apr 28. pii: S1359-6446(15)00154-3. doi:, 10.1016/j.drudis.2015.04.005. PMID:25931264 doi:https://dx.doi.org/10.1016/j.drudis.2015.04.005
