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| | <StructureSection load='6kxr' size='340' side='right'caption='[[6kxr]], [[Resolution|resolution]] 2.45Å' scene=''> | | <StructureSection load='6kxr' size='340' side='right'caption='[[6kxr]], [[Resolution|resolution]] 2.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6kxr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Stra7 Stra7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KXR OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6KXR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6kxr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_ambofaciens_ATCC_23877 Streptomyces ambofaciens ATCC 23877]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KXR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KXR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLT:D-MALATE'>MLT</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4507368Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6kxp|6kxp]], [[6kxh|6kxh]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLT:D-MALATE'>MLT</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SAMT0137, SAMT0138 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=278992 STRA7])</td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6kxr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kxr OCA], [https://pdbe.org/6kxr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kxr RCSB], [https://www.ebi.ac.uk/pdbsum/6kxr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kxr ProSAT]</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 id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6kxr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kxr OCA], [http://pdbe.org/6kxr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kxr RCSB], [http://www.ebi.ac.uk/pdbsum/6kxr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kxr ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/A0A0K2AJY3_STRA7 A0A0K2AJY3_STRA7] |
| - | Epoxide hydrolases (EHs) have been characterized and engineered as biocatalysts that convert epoxides to valuable chiral vicinal diol precursors of drugs and bioactive compounds. Nonetheless, the regioselectivity control of the epoxide ring opening by EHs remains challenging. Alp1U is an alpha/beta-fold EH that exhibits poor regioselectivity in the epoxide hydrolysis of fluostatin C (1), and produces a pair of stereoisomers. Herein, we established the absolute configuration of the two stereoisomeric products and determined the crystal structure of Alp1U. A W186/W187/Y247 oxirane oxygen hole was identified in Alp1U that replaced the canonical Tyr/Tyr pair in alpha/beta-EHs. Mutation of residues in the atypical oxirane oxygen hole of Alp1U improved the regioselectivity for epoxide hydrolysis on 1. The single site Y247F mutation led to highly regioselective (98%) attack at C-3 of 1, while the double mutation W187F/Y247F resulted in regioselective (94%) nucleophilic attack at C-2. Furthermore, single crystal X-ray structures of the two regioselective Alp1U variants in complex with 1 were determined. These findings allowed insights into the reaction details of Alp1U, and provided a new approach for engineering regioselective epoxide hydrolases.
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| - | Mutation of an atypical oxirane oxyanion hole improves regioselectivity of the alpha/beta-fold epoxide hydrolase Alp1U.,Zhang L, De BC, Zhang W, Mandi A, Fang Z, Yang C, Zhu Y, Kurtan T, Zhang C J Biol Chem. 2020 Oct 1. pii: RA120.015563. doi: 10.1074/jbc.RA120.015563. PMID:33004437<ref>PMID:33004437</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 6kxr" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hydrolase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Stra7]] | + | [[Category: Streptomyces ambofaciens ATCC 23877]] |
| - | [[Category: De, B C]] | + | [[Category: De BC]] |
| - | [[Category: Yingli, Z]] | + | [[Category: Yingli Z]] |
| - | [[Category: Zhang, C]] | + | [[Category: Zhang C]] |
| - | [[Category: Zhang, L]] | + | [[Category: Zhang L]] |
| - | [[Category: Cis-vicinal diol]]
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| - | [[Category: Hydrolyse epoxide]]
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