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| <StructureSection load='7odm' size='340' side='right'caption='[[7odm]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='7odm' size='340' side='right'caption='[[7odm]], [[Resolution|resolution]] 2.60Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[7odm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ODM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ODM FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ODM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ODM FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VDW:[(2~{S})-5-[[(2~{R})-1-(2-hydroxy-2-oxoethylamino)-1-oxidanylidene-3-sulfanyl-propan-2-yl]amino]-1-oxidanyl-1,5-bis(oxidanylidene)pentan-2-yl]azanium'>VDW</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]] 2.6Å</td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glutathione_transferase Glutathione transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.18 2.5.1.18] </span></td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VDW:[(2~{S})-5-[[(2~{R})-1-(2-hydroxy-2-oxoethylamino)-1-oxidanylidene-3-sulfanyl-propan-2-yl]amino]-1-oxidanyl-1,5-bis(oxidanylidene)pentan-2-yl]azanium'>VDW</scene></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=7odm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7odm OCA], [https://pdbe.org/7odm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7odm RCSB], [https://www.ebi.ac.uk/pdbsum/7odm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7odm ProSAT]</span></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=7odm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7odm OCA], [https://pdbe.org/7odm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7odm RCSB], [https://www.ebi.ac.uk/pdbsum/7odm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7odm ProSAT]</span></td></tr> |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The evolution and growth of multiple-herbicide resistance (MHR) in grass weeds continues to threaten global cereal production. While various processes can contribute to resistance, earlier work has identified the phi class glutathione-S-transferase (AmGSTF1) as a functional biomarker of MHR in black-grass (Alopecurus myosuroides). This study provides further insights into the role of AmGSTF1 in MHR using a combination of chemical and structural biology. Crystal structures of wild-type AmGSTF1, together with two specifically designed variants that allowed the co-crystal structure determination with glutathione and a glutathione adduct of the AmGSTF1 inhibitor 4-chloro-7-nitro-benzofurazan (NBD-Cl) were obtained. These studies demonstrated that the inhibitory activity of NBD-Cl was associated with the occlusion of the active site and the impediment of substrate binding. A search for other selective inhibitors of AmGSTF1, using ligand-fishing experiments, identified a number of flavonoids as potential ligands. Subsequent experiments using black-grass extracts discovered a specific flavonoid as a natural ligand of the recombinant enzyme. A series of related synthetic flavonoids was prepared and their binding to AmGSTF1 was investigated showing a high affinity for derivatives bearing a O-5-decyl-alpha-carboxylate. Molecular modelling based on high-resolution crystal structures allowed a binding pose to be defined which explained flavonoid binding specificity. Crucially, high binding affinity was linked to a reversal of the herbicide resistance phenotype in MHR black-grass. Collectively, these results present a nature-inspired new lead for the development of herbicide synergists to counteract MHR in weeds.
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| Flavonoid-based inhibitors of the Phi-class glutathione transferase from black-grass to combat multiple herbicide resistance.,Schwarz M, Eno RFM, Freitag-Pohl S, Coxon CR, Straker HE, Wortley DJ, Hughes DJ, Mitchell G, Moore J, Cummins I, Onkokesung N, Brazier-Hicks M, Edwards R, Pohl E, Steel PG Org Biomol Chem. 2021 Nov 3;19(42):9211-9222. doi: 10.1039/d1ob01802g. PMID:34643629<ref>PMID:34643629</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 7odm" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Glutathione transferase]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Eno, R F.M]] | | [[Category: Eno RFM]] |
| [[Category: Pohl, E]] | | [[Category: Pohl E]] |
| [[Category: Glutathione]]
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| [[Category: Glutathione-s-transferase]]
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| [[Category: Transferase]]
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