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Epoxide hydrolase

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<StructureSection load='5alf' size='400' side='right' caption='Human soluble epoxide hydrolase complex with imidazole derivative inhibitor (PDB code [[5alf]])' scene='70/708145/Cv/1'>
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<StructureSection load='' size='350' side='right' caption='Human soluble epoxide hydrolase complex with imidazole derivative inhibitor (PDB code [[5alf]])' scene='70/708145/Cv/1'>
== Function ==
== Function ==
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'''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<ref>PMID:18585390</ref>.<br /> '''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.<br /> '''Limonene-1,2-epoxide hydrolase''' catalyzes the conversion of limonene-1,2-epoxide to limonene-1,2-diol<ref>PMID:12773375</ref> .
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'''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<ref>PMID:18585390</ref>.<br /> '''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.<br /> '''Limonene-1,2-epoxide hydrolase''' catalyzes the conversion of limonene-1,2-epoxide to limonene-1,2-diol<ref>PMID:12773375</ref> . For details see [[limonene-1,2-epoxide hydrolase]].
== Disease ==
== Disease ==
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== Structural highlights ==
== Structural highlights ==
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<scene name='70/708145/Cv/2'>Biological assembly of Human soluble epoxide hydrolase is dimer</scene>.
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<scene name='70/708145/Cv/6'>Biological assembly of Human soluble epoxide hydrolase is dimer</scene>.
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<scene name='70/708145/Cv/5'>Inhibitor binding site</scene> (PDB code [[5alf]]).<ref>PMID:25931264</ref>
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<scene name='70/708145/Cv/7'>Inhibitor binding site</scene> (PDB code [[5alf]]).<ref>PMID:25931264</ref>
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</StructureSection>
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== 3D Structures of epoxide hydrolase==
== 3D Structures of epoxide hydrolase==
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[[Epoxide hydrolase 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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</StructureSection>
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*Epoxide hydrolase
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**[[2e3j]] – EH B – ''Mycobacterium tuberculosis''<br />
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**[[1qo7]], [[3g02]] – AnEH (mutant) – ''Aspergillus niger''<br />
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**[[2cjp]] – pEH I – potato<br />
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**[[3cxu]] – pEH (mutant) <br />
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**[[4i19]], [[4qa9]] – EH – ''Streptomyces carzinostaticus''<br />
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*Soluble epoxide hydrolase
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**[[1s8o]], [[3i1y]], [[3i28]], [[3koo]], [[5ahx]] – hSEH – human<br />
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**[[1cqz]] – mSEH – mouse<br />
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**[[4nzz]] – BmSEH – ''Bacillus megaterium''<br />
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**[[4inz]] – BmSEH (mutant) <br />
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**[[1ehy]] – SEH – ''Agrobacterium tumefaciens''<br />
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*Epoxide hydrolase complex with inhibitor
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**[[3g0i]] – AnEH + valpromide<br />
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**[[3rga]] – SlEH + oxazolidinone inhibitor – ''Streptomyces lasaliensis''<br />
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**[[4rzm]] – SlEH + lasalocid A<br />
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*Soluble epoxide hydrolase complex with inhibitor
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**[[1vj5]], [[1zd2]], [[1zd3]], [[1zd4]], [[1zd5]], [[3wk4]], [[4c4x]], [[4c4y]], [[4c4z]], [[5ai5]], [[5akz]], [[5ali]] – hSEH + urea derivative inhibitor<br />
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**[[1cr6]], [[1ek1]], [[1ek2]] – mSEH + urea derivative inhibitor<br />
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**[[3otq]], [[3wk7]], [[4y2j]], [[4y2s]], [[4y2v]], [[5ak4]], [[5akh]], [[5aki]], [[5alk]], [[5alq]], [[5alv]], [[5aly]] – hSEH + pyrazole inhibitor<br />
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**[[5akj]], [[5alf]], [[5als]] – hSEH + imidazole inhibitor<br />
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**[[5akk]], [[5ald]], [[5aln]], [[5alo]], [[5alw]], [[5am4]] – hSEH + indolone inhibitor<br />
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**[[5akx]], [[5aky]] – hSEH + indazole inhibitor<br />
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**[[3wk5]], [[3wk6]], [[3wk8]], [[3wk9]], [[3wkc]], [[5ai8]], [[5aic]], [[5akg]], [[5alg]] – hSEH + thiazole derivative inhibitor<br />
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**[[3ans]], [[3ant]] – hSEH + synthetic inhibitor<br />
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**[[3pdc]], [[5ale]] – hSEH catalytic domain + benzoxazole inhibitor<br />
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**[[4jnc]], [[5alx]] – hSEH catalytic domain + carboxamide inhibitor<br />
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**[[4x6x]], [[4x6y]] – hSEH catalytic domain + cyclopropane inhibitor<br />
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**[[4hai]], [[3wka]], [[4ocz]], [[4od0]], [[5ake]], [[5alh]], [[5am1]] – hSEH + piperidine derivative inhibitor<br />
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**[[4y2p]], [[4y2q]], [[5ai4]], [[5ak5]], [[5ak6]], [[5alt]], [[5am5]] – hSEH + pyridine derivative inhibitor<br />
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**[[4y2r]] – hSEH + piperazine derivative inhibitor<br />
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**[[5akl]], [[5alm]], [[5am0]] – hSEH + pyrrolidine derivative inhibitor<br />
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**[[4y2t]], [[5aib]] – hSEH + benzyloxy derivative inhibitor<br />
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**[[3wkb]] – hSEH + quinoxaline derivative inhibitor<br />
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**[[4y2u]], [[5ai6]], [[5alj]], [[5alr]], [[5am2]] – hSEH + quinoline derivative inhibitor<br />
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**[[4y2x]], [[5alu]], [[5alz]] – hSEH + adamantanyl derivative inhibitor<br />
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**[[4y2y]] – hSEH + etylmethyamine derivative inhibitor<br />
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**[[3wkd]], [[5alp]] – hSEH + morpholine derivative inhibitor<br />
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**[[3wke]], [[5am3]] – hSEH + carbamoyl derivative inhibitor<br />
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**[[4j03]] – hSEH + fulvestrant<br />
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**[[5ai0]] – hSEH + phenyl oxadiazolamine inhibitor<br />
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**[[5ai9]] – hSEH + phenol derivative inhibitor<br />
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**[[5aia]] – hSEH + benzoate derivative inhibitor<br />
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**[[5ak3]] – hSEH + indan-amine derivative inhibitor<br />
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**[[5all]] – hSEH + cyclohexyl methanol inhibitor<br />
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**[[4o08]] – BmSEH + phenoxy acetamide inhibitor<br />
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*Soluble epoxide hydrolase complex with product
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**[[4io0]] – BmSEH + naphthyloxy propane diol<br />
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*Limonene-1,2-epoxide hydrolase
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**[[1nww]] – ReEH – ''Rhodococcus erythropolis''<br />
 
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**[[4r9k]], [[4r9l]], [[4xbx]], [[4xdw]] – ReEH (mutant)<br />
 
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**[[1nu3]] – ReEH + valpromide <br />
 
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**[[4xbt]], [[4xdv]] – ReEH (mutant) + cyclohexanediol<br />
 
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**[[4xby]] – ReEH (mutant) + cyclopentene oxi
 
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}}
 
== References ==
== References ==
<references/>
<references/>
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[[Category:Topic Page]]

Current revision

Human soluble epoxide hydrolase complex with imidazole derivative inhibitor (PDB code 5alf)

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References

  1. ↑ 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
  2. ↑ 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:http://dx.doi.org/10.1093/emboj/cdg275
  3. ↑ 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:http://dx.doi.org/10.1038/nrd2875
  4. ↑ 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:http://dx.doi.org/10.1016/j.drudis.2015.04.005

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Michal Harel, Alexander Berchansky, Joel L. Sussman

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