6d4o

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Current revision (14:32, 13 March 2024) (edit) (undo)
 
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<StructureSection load='6d4o' size='340' side='right'caption='[[6d4o]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
<StructureSection load='6d4o' size='340' side='right'caption='[[6d4o]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6d4o]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_27750 Atcc 27750]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D4O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D4O FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6d4o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lachnospira_eligens Lachnospira eligens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D4O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D4O 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUV:(5aR,9aR)-2-chloro-11-(4-beta-D-glucopyranuronosylpiperazin-1-yl)-5a,6,9,9a-tetrahydrodibenzo[b,f][1,4]oxazepine'>FUV</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 2.9&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">uidA, ERS852490_00568, ERS852492_02599 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=39485 ATCC 27750])</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUV:(5aR,9aR)-2-chloro-11-(4-beta-D-glucopyranuronosylpiperazin-1-yl)-5a,6,9,9a-tetrahydrodibenzo[b,f][1,4]oxazepine'>FUV</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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/Beta-glucuronidase Beta-glucuronidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.31 3.2.1.31] </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=6d4o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d4o OCA], [https://pdbe.org/6d4o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d4o RCSB], [https://www.ebi.ac.uk/pdbsum/6d4o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d4o 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=6d4o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d4o OCA], [http://pdbe.org/6d4o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d4o RCSB], [http://www.ebi.ac.uk/pdbsum/6d4o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d4o 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/A0A174ZZA3_9FIRM A0A174ZZA3_9FIRM]
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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.
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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>
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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 6d4o" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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*[[Galactosidase 3D structures|Galactosidase 3D structures]]
*[[Glucuronisidase 3D structures|Glucuronisidase 3D structures]]
*[[Glucuronisidase 3D structures|Glucuronisidase 3D structures]]
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Atcc 27750]]
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[[Category: Lachnospira eligens]]
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[[Category: Beta-glucuronidase]]
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[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Pellock, S J]]
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[[Category: Pellock SJ]]
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[[Category: Redinbo, M R]]
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[[Category: Redinbo MR]]
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[[Category: Walton, W G]]
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[[Category: Walton WG]]
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[[Category: Glycosyl hydrolase]]
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[[Category: Hydrolase]]
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Current revision

Eubacterium eligens beta-glucuronidase bound to an amoxapine-glucuronide conjugate

PDB ID 6d4o

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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