View source for 6ldc


==Structure of Bifidobacterium dentium beta-glucuronidase complexed with C6-nonyl uronic isofagomine==
<StructureSection load='6ldc' size='340' side='right'caption='[[6ldc]], [[Resolution|resolution]] 2.18&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ldc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bifidobacterium_dentium_Bd1 Bifidobacterium dentium Bd1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LDC 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]] 2.181&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E9O:(2~{S},3~{S},4~{R},5~{R})-2-nonyl-4,5-bis(oxidanyl)piperidine-3-carboxylic+acid'>E9O</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=6ldc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ldc OCA], [https://pdbe.org/6ldc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ldc RCSB], [https://www.ebi.ac.uk/pdbsum/6ldc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ldc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/D2Q7B1_BIFDB D2Q7B1_BIFDB] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Irinotecan inhibits cell proliferation and thus is used for the primary treatment of colorectal cancer. Metabolism of irinotecan involves incorporation of beta-glucuronic acid to facilitate excretion. During transit of the glucuronidated product through the gastrointestinal tract, an induced upregulation of gut microbial beta-glucuronidase (GUS) activity may cause severe diarrhea and thus force many patients to stop treatment. We herein report the development of uronic isofagomine (UIFG) derivatives that act as general, potent inhibitors of bacterial GUSs, especially those of Escherichia coli and Clostridium perfringens. The best inhibitor, C6-nonyl UIFG, is 23,300-fold more selective for E. coli GUS than for human GUS (Ki = 0.0045 and 105 muM, respectively). Structural evidence indicated that the loss of coordinated water molecules, with the consequent increase in entropy, contributes to the high affinity and selectivity for bacterial GUSs. The inhibitors also effectively reduced irinotecan-induced diarrhea in mice without damaging intestinal epithelial cells.

Entropy-driven binding of gut bacterial beta-glucuronidase inhibitors ameliorates irinotecan-induced toxicity.,Lin HY, Chen CY, Lin TC, Yeh LF, Hsieh WC, Gao S, Burnouf PA, Chen BM, Hsieh TJ, Dashnyam P, Kuo YH, Tu Z, Roffler SR, Lin CH Commun Biol. 2021 Mar 4;4(1):280. doi: 10.1038/s42003-021-01815-w. PMID:33664385<ref>PMID:33664385</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ldc" style="background-color:#fffaf0;"></div>

==See Also==
*[[Galactosidase 3D structures|Galactosidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bifidobacterium dentium Bd1]]
[[Category: Large Structures]]
[[Category: Hsieh T-J]]
[[Category: Lin C-H]]
[[Category: Lin H-Y]]