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| | <StructureSection load='6d7f' size='340' side='right'caption='[[6d7f]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='6d7f' size='340' side='right'caption='[[6d7f]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6d7f]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_8492 Atcc 8492]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D7F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D7F FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6d7f]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_uniformis Bacteroides uniformis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D7F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D7F FirstGlance]. <br> |
| - | </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=FYJ:phenyl+1-thio-beta-D-glucopyranosiduronic+acid'>FYJ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.4Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">uidA_4, ERS417307_01040 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=820 ATCC 8492])</td></tr> | + | <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=FYJ:phenyl+1-thio-beta-D-glucopyranosiduronic+acid'>FYJ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <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> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6d7f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d7f OCA], [https://pdbe.org/6d7f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d7f RCSB], [https://www.ebi.ac.uk/pdbsum/6d7f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d7f ProSAT]</span></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=6d7f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d7f OCA], [http://pdbe.org/6d7f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d7f RCSB], [http://www.ebi.ac.uk/pdbsum/6d7f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d7f ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/A0A174CQK8_BACUN A0A174CQK8_BACUN] |
| - | The carbohydrates and glycoconjugates that enter the human gastrointestinal tract (GI) are remarkably complex, and most of the genes encoding the enzymes required for processing these molecules are not present in the human genome. The glycoside hydrolases encoded by the human gut microbiome therefore play an integral role in processing these diverse exogenous and endogenous glycoconjugates. Here, we analyzed three structurally and functionally distinct beta-glucuronidase (GUS) glycoside hydrolases from a single commensal microbe of the human gut, Bacteroides uniformis. Using nine crystal structures and biochemical and biophysical data, we show that although these three proteins share similar overall folds, they exhibit different structural features that create three structurally and functionally unique active sites. Notably, we found that quaternary structure plays an important role in creating distinct active-site features that are difficult to predict via structural modeling methods alone. The enzymes displayed differential processing capabilities toward several glucuronic acid-containing polysaccharides. They also hydrolyzed SN-38-glucuronide, a metabolite of the anticancer drug irinotecan, suggesting that these gut-microbial enzymes could reactivate this drug in the GI. We further demonstrate that GUS-specific and non-selective inhibitors exhibit varying potencies toward each enzyme. Together, these results highlight the diversity of GUS enzymes within a single Bacteroides gut commensal and advance our understanding of how structural properties affect the specific roles of microbial enzymes in processing and catabolizing drug-derived glucuronides and glycan substrates.
| + | |
| | | | |
| - | Three structurally and functionally distinct beta-glucuronidases from the human gut microbe Bacteroides uniformis.,Pellock SJ, Walton WG, Biernat KA, Torres-Rivera D, Creekmore BC, Xu Y, Liu J, Tripathy A, Stewart LJ, Redinbo MR J Biol Chem. 2018 Oct 9. pii: RA118.005414. doi: 10.1074/jbc.RA118.005414. PMID:30301767<ref>PMID:30301767</ref>
| + | ==See Also== |
| - | | + | *[[Glucuronisidase 3D structures|Glucuronisidase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6d7f" style="background-color:#fffaf0;"></div>
| + | |
| - | == References == | + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 8492]] | + | [[Category: Bacteroides uniformis]] |
| - | [[Category: Beta-glucuronidase]]
| + | |
| | [[Category: Large Structures]] | | [[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: Glycosyl hydrolase 2]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
