1ek1: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1ek1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EK1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EK1 FirstGlance]. <br> | <table><tr><td colspan='2'>[[1ek1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EK1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EK1 FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIU:N-CYCLOHEXYL-N-(4-IODOPHENYL)UREA'>CIU</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIU:N-CYCLOHEXYL-N-(4-IODOPHENYL)UREA'>CIU</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1cqz|1cqz]], [[1cr6|1cr6]], [[1ek2|1ek2]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1cqz|1cqz]], [[1cr6|1cr6]], [[1ek2|1ek2]]</td></tr> | ||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.9 and 3.3.2.10 3.3.2.9 and 3.3.2.10] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.9 and 3.3.2.10 3.3.2.9 and 3.3.2.10] </span></td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ek1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ek1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ek1 RCSB], [http://www.ebi.ac.uk/pdbsum/1ek1 PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ek1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ek1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ek1 RCSB], [http://www.ebi.ac.uk/pdbsum/1ek1 PDBsum]</span></td></tr> | ||
<table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Argiriadi, M A | [[Category: Argiriadi, M A]] | ||
[[Category: Christianson, D W | [[Category: Christianson, D W]] | ||
[[Category: Dowdy, D L | [[Category: Dowdy, D L]] | ||
[[Category: Goodrow, M H | [[Category: Goodrow, M H]] | ||
[[Category: Hammock, B D | [[Category: Hammock, B D]] | ||
[[Category: Morisseau, C | [[Category: Morisseau, C]] | ||
[[Category: Alpha/beta hydrolase fold]] | [[Category: Alpha/beta hydrolase fold]] | ||
[[Category: Disubstituted urea inhibitor]] | [[Category: Disubstituted urea inhibitor]] | ||
[[Category: Homodimer]] | [[Category: Homodimer]] | ||
Revision as of 01:20, 23 December 2014
CRYSTAL STRUCTURE OF MURINE SOLUBLE EPOXIDE HYDROLASE COMPLEXED WITH CIU INHIBITORCRYSTAL STRUCTURE OF MURINE SOLUBLE EPOXIDE HYDROLASE COMPLEXED WITH CIU INHIBITOR
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. 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:10747889[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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