1ek2

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[[Image:1ek2.gif|left|200px]]<br /><applet load="1ek2" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1ek2, resolution 3.0&Aring;" />
 
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'''CRYSTAL STRUCTURE OF MURINE SOLUBLE EPOXIDE HYDROLASE COMPLEXED WITH CDU INHIBITOR'''<br />
 
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==Overview==
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==CRYSTAL STRUCTURE OF MURINE SOLUBLE EPOXIDE HYDROLASE COMPLEXED WITH CDU INHIBITOR==
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The structures of two alkylurea inhibitors complexed with murine soluble epoxide hydrolase have been determined by x-ray crystallographic methods. The alkyl substituents of each inhibitor make extensive hydrophobic contacts in the soluble epoxide hydrolase active site, and each urea carbonyl oxygen accepts hydrogen bonds from the phenolic hydroxyl groups of Tyr(381) and Tyr(465). These hydrogen bond interactions suggest that Tyr(381) and/or Tyr(465) are general acid catalysts that facilitate epoxide ring opening in the first step of the hydrolysis reaction; Tyr(465) is highly conserved among all epoxide hydrolases, and Tyr(381) is conserved among the soluble epoxide hydrolases. In one enzyme-inhibitor complex, the urea carbonyl oxygen additionally interacts with Gln(382). If a comparable interaction occurs in catalysis, then Gln(382) may provide electrostatic stabilization of partial negative charge on the epoxide oxygen. The carboxylate side chain of Asp(333) accepts a hydrogen bond from one of the urea NH groups in each enzyme-inhibitor complex. Because Asp(333) is the catalytic nucleophile, its interaction with the partial positive charge on the urea NH group mimics its approach toward the partial positive charge on the electrophilic carbon of an epoxide substrate. Accordingly, alkylurea inhibitors mimic features encountered in the reaction coordinate of epoxide ring opening, and a structure-based mechanism is proposed for leukotoxin epoxide hydrolysis.
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<StructureSection load='1ek2' size='340' side='right'caption='[[1ek2]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1ek2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EK2 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CDU:N-CYCLOHEXYL-N-DECYLUREA'>CDU</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ek2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ek2 OCA], [https://pdbe.org/1ek2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ek2 RCSB], [https://www.ebi.ac.uk/pdbsum/1ek2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ek2 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/HYES_MOUSE HYES_MOUSE] 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 (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ek/1ek2_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ek2 ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1EK2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=CDU:'>CDU</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Microsomal_epoxide_hydrolase Microsomal epoxide hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.9 3.3.2.9] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EK2 OCA].
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*[[Epoxide hydrolase 3D structures|Epoxide hydrolase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Binding of alkylurea inhibitors to epoxide hydrolase implicates active site tyrosines in substrate activation., Argiriadi MA, Morisseau C, Goodrow MH, Dowdy DL, Hammock BD, Christianson DW, J Biol Chem. 2000 May 19;275(20):15265-70. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10747889 10747889]
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[[Category: Large Structures]]
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[[Category: Microsomal epoxide hydrolase]]
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[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Single protein]]
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[[Category: Argiriadi MA]]
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[[Category: Argiriadi, M A.]]
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[[Category: Christianson DW]]
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[[Category: Christianson, D W.]]
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[[Category: Dowdy DL]]
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[[Category: Dowdy, D L.]]
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[[Category: Goodrow MH]]
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[[Category: Goodrow, M H.]]
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[[Category: Hammock BD]]
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[[Category: Hammock, B D.]]
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[[Category: Morisseau C]]
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[[Category: Morisseau, C.]]
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[[Category: CDU]]
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[[Category: alpha/beta hydrolase fold]]
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[[Category: disubstituted urea inhibitor]]
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[[Category: homodimer]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:28:38 2008''
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Current revision

CRYSTAL STRUCTURE OF MURINE SOLUBLE EPOXIDE HYDROLASE COMPLEXED WITH CDU INHIBITOR

PDB ID 1ek2

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