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| | ==Clostridium perfringens putative fatty acid metabolism regulator== | | ==Clostridium perfringens putative fatty acid metabolism regulator== |
| - | <StructureSection load='6azh' size='340' side='right' caption='[[6azh]], [[Resolution|resolution]] 1.75Å' scene=''> | + | <StructureSection load='6azh' size='340' side='right'caption='[[6azh]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6azh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_perfringens"_veillon_and_zuber_1898 "bacillus perfringens" veillon and zuber 1898]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AZH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AZH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6azh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_perfringens Clostridium perfringens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AZH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AZH FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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]] 1.75Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BXT94_00180 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1502 "Bacillus perfringens" Veillon and Zuber 1898])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=6azh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6azh OCA], [http://pdbe.org/6azh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6azh RCSB], [http://www.ebi.ac.uk/pdbsum/6azh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6azh 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=6azh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6azh OCA], [https://pdbe.org/6azh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6azh RCSB], [https://www.ebi.ac.uk/pdbsum/6azh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6azh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus perfringens veillon and zuber 1898]] | + | [[Category: Clostridium perfringens]] |
| - | [[Category: Redinbo, M R]] | + | [[Category: Large Structures]] |
| - | [[Category: William, W G]] | + | [[Category: Redinbo MR]] |
| - | [[Category: Regulator]] | + | [[Category: William WG]] |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Publication Abstract from PubMed
The gut microbiota harbor diverse beta-glucuronidase (GUS) enzymes that liberate glucuronic acid (GlcA) sugars from small-molecule conjugates and complex carbohydrates. However, only the Enterobacteriaceae family of human gut-associated Proteobacteria maintain a GUS operon under the transcriptional control of a glucuronide repressor, GusR. Despite its potential importance in Escherichia, Salmonella, Klebsiella, Shigella, and Yersinia opportunistic pathogens, the structure of GusR has not been examined. Here, we explore the molecular basis for GusR-mediated regulation of GUS expression in response to small-molecule glucuronides. Presented are 2.1-A-resolution crystal structures of GusRs from Escherichia coli and Salmonella enterica in complexes with a glucuronide ligand. The GusR-specific DNA operator site in the regulatory region of the E. coli GUS operon is identified, and structure-guided GusR mutants pinpoint the residues essential for DNA binding and glucuronide recognition. Interestingly, the endobiotic estradiol-17-glucuronide and the xenobiotic indomethacin-acyl-glucuronide are found to exhibit markedly differential binding to these GusR orthologs. Using structure-guided mutations, we are able to transfer E. coli GusR's preferential DNA and glucuronide binding affinity to S. enterica GusR. Structures of putative GusR orthologs from GUS-encoding Firmicutes species also reveal functionally unique features of the Enterobacteriaceae GusRs. Finally, dominant-negative GusR variants are validated in cell-based studies. These data provide a molecular framework toward understanding the control of glucuronide utilization by opportunistic pathogens in the human gut.
Structural basis for the regulation of beta-glucuronidase expression by human gut Enterobacteriaceae.,Little MS, Pellock SJ, Walton WG, Tripathy A, Redinbo MR Proc Natl Acad Sci U S A. 2017 Dec 21. pii: 1716241115. doi:, 10.1073/pnas.1716241115. PMID:29269393[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Little MS, Pellock SJ, Walton WG, Tripathy A, Redinbo MR. Structural basis for the regulation of beta-glucuronidase expression by human gut Enterobacteriaceae. Proc Natl Acad Sci U S A. 2017 Dec 21. pii: 1716241115. doi:, 10.1073/pnas.1716241115. PMID:29269393 doi:http://dx.doi.org/10.1073/pnas.1716241115
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