4o08

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==Crystal structure of bacillus megaterium epoxide hydrolase in complex with an inhibitor==
==Crystal structure of bacillus megaterium epoxide hydrolase in complex with an inhibitor==
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<StructureSection load='4o08' size='340' side='right' caption='[[4o08]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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<StructureSection load='4o08' size='340' side='right'caption='[[4o08]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4o08]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O08 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O08 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4o08]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Priestia_megaterium Priestia megaterium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O08 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4O08 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO6:2-PHENOXYACETAMIDE'>PO6</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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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]] 1.95&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nzz|4nzz]]</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=PO6:2-PHENOXYACETAMIDE'>PO6</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pyrimidine-5'-nucleotide_nucleosidase Pyrimidine-5'-nucleotide nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.10 3.2.2.10] </span></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=4o08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o08 OCA], [https://pdbe.org/4o08 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4o08 RCSB], [https://www.ebi.ac.uk/pdbsum/4o08 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4o08 ProSAT]</span></td></tr>
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<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=4o08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o08 OCA], [http://pdbe.org/4o08 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o08 RCSB], [http://www.ebi.ac.uk/pdbsum/4o08 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o08 ProSAT]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/G9BEX6_PRIMG G9BEX6_PRIMG]
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Optically pure epoxides are essential chiral precursors for the production of (S)-propranolol, (S)-alprenolol, and other beta-adrenergic receptor blocking drugs. Although the enzymatic production of these bulky epoxides has proven difficult, here we report a method to effectively improve the activity of BmEH, an epoxide hydrolase from Bacillus megaterium ECU1001 toward alpha-naphthyl glycidyl ether, the precursor of (S)-propranolol, by eliminating the steric hindrance near the potential product-release site. Using X-ray crystallography, mass spectrum, and molecular dynamics calculations, we have identified an active tunnel for substrate access and product release of this enzyme. The crystal structures revealed that there is an independent product-release site in BmEH that was not included in other reported epoxide hydrolase structures. By alanine scanning, two mutants, F128A and M145A, targeted to expand the potential product-release site displayed 42 and 25 times higher activities toward alpha-naphthyl glycidyl ether than the wild-type enzyme, respectively. These results show great promise for structure-based rational design in improving the catalytic efficiency of industrial enzymes for bulky substrates.
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Engineering of an epoxide hydrolase for efficient bioresolution of bulky pharmaco substrates.,Kong XD, Yuan S, Li L, Chen S, Xu JH, Zhou J Proc Natl Acad Sci U S A. 2014 Nov 4;111(44):15717-22. doi:, 10.1073/pnas.1404915111. Epub 2014 Oct 20. PMID:25331869<ref>PMID:25331869</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4o08" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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*[[Epoxide hydrolase|Epoxide hydrolase]]
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*[[Epoxide hydrolase 3D structures|Epoxide hydrolase 3D structures]]
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Pyrimidine-5'-nucleotide nucleosidase]]
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[[Category: Large Structures]]
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[[Category: Kong, X D]]
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[[Category: Priestia megaterium]]
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[[Category: Xu, J H]]
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[[Category: Kong XD]]
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[[Category: Zhou, J H]]
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[[Category: Xu JH]]
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[[Category: A/b hydrolase fold]]
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[[Category: Zhou JH]]
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[[Category: Epoxide hydrolase]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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Current revision

Crystal structure of bacillus megaterium epoxide hydrolase in complex with an inhibitor

PDB ID 4o08

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