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6bo6

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Eubacterium eligens beta-glucuronidase bound to UNC4917 glucuronic acid conjugate

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Retrieved from "http://52.214.119.220/wiki/index.php/6bo6"

Categories: Large Structures | Pellock SJ | Redinbo MR | Walton WG

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 <StructureSection load='6bo6' size='340' side='right'caption='[[6bo6]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6bo6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Eube2 Eube2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BO6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BO6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6bo6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Eubacterium_eligens_ATCC_27750 Eubacterium eligens ATCC 27750]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BO6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BO6 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E0V:4-(4-beta-D-glucopyranuronosylpiperazin-1-yl)-2,7-bis(methylamino)pyrido[3,2 4,5]thieno[3,2-d]pyrimidine'>E0V</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]] 2.801&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EUBELI_20590 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=515620 EUBE2])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E0V:4-(4-beta-D-glucopyranuronosylpiperazin-1-yl)-2,7-bis(methylamino)pyrido[3,2 4,5]thieno[3,2-d]pyrimidine'>E0V</scene></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=6bo6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bo6 OCA], [http://pdbe.org/6bo6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bo6 RCSB], [http://www.ebi.ac.uk/pdbsum/6bo6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bo6 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=6bo6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bo6 OCA], [https://pdbe.org/6bo6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bo6 RCSB], [https://www.ebi.ac.uk/pdbsum/6bo6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bo6 ProSAT]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
+== Function ==
-== Publication Abstract from PubMed ==
+[https://www.uniprot.org/uniprot/C4Z6Z2_LACE2 C4Z6Z2_LACE2]
-Microbial beta-glucuronidases (GUSs) cause severe gut toxicities that limit the efficacy of cancer drugs and other therapeutics. Selective inhibitors of bacterial GUS have been shown to alleviate these side effects. Using structural and chemical biology, mass spectrometry, and cell-based assays, we establish that piperazine-containing GUS inhibitors intercept the glycosyl-enzyme catalytic intermediate of these retaining glycosyl hydrolases. We demonstrate that piperazine-based compounds are substrate-dependent GUS inhibitors that bind to the GUS-GlcA catalytic intermediate as a piperazine-linked glucuronide (GlcA, glucuronic acid). We confirm the GUS-dependent formation of inhibitor-glucuronide conjugates by LC-MS and show that methylated piperazine analogs display significantly reduced potencies. We further demonstrate that a range of approved piperazine- and piperidine-containing drugs from many classes, including those for the treatment of depression, infection, and cancer, function by the same mechanism, and we confirm through gene editing that these compounds selectively inhibit GUS in living bacterial cells. Together, these data reveal a unique mechanism of GUS inhibition and show that a range of therapeutics may impact GUS activities in the human gut.
-Gut Microbial beta-Glucuronidase Inhibition via Catalytic Cycle Interception.,Pellock SJ, Creekmore BC, Walton WG, Mehta N, Biernat KA, Cesmat AP, Ariyarathna Y, Dunn ZD, Li B, Jin J, James LI, Redinbo MR ACS Cent Sci. 2018 Jul 25;4(7):868-879. doi: 10.1021/acscentsci.8b00239. Epub, 2018 Jul 12. PMID:30062115<ref>PMID:30062115</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 6bo6" style="background-color:#fffaf0;"></div>
-== References ==
-<references/>
 __TOC__
 </StructureSection>
-[[Category: Eube2]]
 [[Category: Large Structures]]
-[[Category: Pellock, S J]]
+[[Category: Pellock SJ]]
-[[Category: Redinbo, M R]]
+[[Category: Redinbo MR]]
-[[Category: Walton, W G]]
+[[Category: Walton WG]]
-[[Category: Beta-glucuronidase]]
-[[Category: Glycosyl hydrolase]]
-[[Category: Hormone]]
-[[Category: Hydrolase]]

6bo6

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Eubacterium eligens beta-glucuronidase bound to UNC4917 glucuronic acid conjugate

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