View source for 6bjw


==Eubacterium eligens Beta-glucuronidase==
<StructureSection load='6bjw' size='340' side='right'caption='[[6bjw]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6bjw]] 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=6BJW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BJW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</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=6bjw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bjw OCA], [https://pdbe.org/6bjw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bjw RCSB], [https://www.ebi.ac.uk/pdbsum/6bjw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bjw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C4Z6Z2_LACE2 C4Z6Z2_LACE2] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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 6bjw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glucuronisidase 3D structures|Glucuronisidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pellock SJ]]
[[Category: Redinbo MR]]
[[Category: Walton WG]]