6ayi

<StructureSection load='6ayi' size='340' side='right' caption='[[6ayi]], [[Resolution|resolution]] 2.09&Aring;' scene=''>

<table><tr><td colspan='2'>[[6ayi]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Eco57 Eco57]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AYI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AYI FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C3G:4-nitrophenyl+beta-D-glucopyranosiduronic+acid'>C3G</scene></td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">uidR, Z2623, ECs2326 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83334 ECO57])</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=6ayi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ayi OCA], [http://pdbe.org/6ayi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ayi RCSB], [http://www.ebi.ac.uk/pdbsum/6ayi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ayi ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/UIDR_ECO57 UIDR_ECO57]] Repressor for the uidRABC (gusRABC) operon.

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.

 

== References ==

[[Category: Eco57]]

[[Category: Little, M S]]

[[Category: Pellock, S J]]

[[Category: Dna binding protein]]

[[Category: Glucuronide binding protein]]

[[Category: Transcriptional repressor protein]]