View source for 5czk


==Structure of E. coli beta-glucuronidase bound with a novel, potent inhibitor 1-((6,8-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl)-1-(2-hydroxyethyl)-3-(4-hydroxyphenyl)thiourea==
<StructureSection load='5czk' size='340' side='right'caption='[[5czk]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5czk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CZK 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]] 2.39&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=57Z:1-[(6,8-DIMETHYL-2-OXO-1,2-DIHYDROQUINOLIN-3-YL)METHYL]-1-(2-HYDROXYETHYL)-3-(4-HYDROXYPHENYL)THIOUREA'>57Z</scene>, <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'>[https://proteopedia.org/fgij/fg.htm?mol=5czk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5czk OCA], [https://pdbe.org/5czk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5czk RCSB], [https://www.ebi.ac.uk/pdbsum/5czk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5czk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BGLR_ECOLI BGLR_ECOLI] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The selective inhibition of bacterial beta-glucuronidases was recently shown to alleviate drug-induced gastrointestinal toxicity in mice, including the damage caused by the widely used anticancer drug irinotecan. Here, we report crystal structures of representative beta-glucuronidases from the Firmicutes Streptococcus agalactiae and Clostridium perfringens and the Proteobacterium Escherichia coli, and the characterization of a beta-glucuronidase from the Bacteroidetes Bacteroides fragilis. While largely similar in structure, these enzymes exhibit marked differences in catalytic properties and propensities for inhibition, indicating that the microbiome maintains functional diversity in orthologous enzymes. Small changes in the structure of designed inhibitors can induce significant conformational changes in the beta-glucuronidase active site. Finally, we establish that beta-glucuronidase inhibition does not alter the serum pharmacokinetics of irinotecan or its metabolites in mice. Together, the data presented advance our in vitro and in vivo understanding of the microbial beta-glucuronidases, a promising new set of targets for controlling drug-induced gastrointestinal toxicity.

Structure and Inhibition of Microbiome beta-Glucuronidases Essential to the Alleviation of Cancer Drug Toxicity.,Wallace BD, Roberts AB, Pollet RM, Ingle JD, Biernat KA, Pellock SJ, Venkatesh MK, Guthrie L, O'Neal SK, Robinson SJ, Dollinger M, Figueroa E, McShane SR, Cohen RD, Jin J, Frye SV, Zamboni WC, Pepe-Ranney C, Mani S, Kelly L, Redinbo MR Chem Biol. 2015 Sep 17;22(9):1238-49. doi: 10.1016/j.chembiol.2015.08.005. Epub, 2015 Sep 10. PMID:26364932<ref>PMID:26364932</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5czk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glucuronisidase 3D structures|Glucuronisidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Redinbo MR]]
[[Category: Roberts AR]]
[[Category: Wallace BR]]