View source for 6jz7


==b-glucuronidase from Ruminococcus gnavus in complex with N1-substituted uronic isofagomine==
<StructureSection load='6jz7' size='340' side='right'caption='[[6jz7]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6jz7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ruminococcus_gnavus Ruminococcus gnavus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JZ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JZ7 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]] 1.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CKU:(3~{S},4~{R},5~{R})-4,5-bis(oxidanyl)-1-propyl-piperidine-3-carboxylic+acid'>CKU</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=6jz7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jz7 OCA], [https://pdbe.org/6jz7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jz7 RCSB], [https://www.ebi.ac.uk/pdbsum/6jz7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jz7 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q6W7J7_RUMGN Q6W7J7_RUMGN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Selective inhibitors of gut bacterial beta-glucuronidases (GUSs) are of particular interest in the prevention of xenobiotic-induced toxicities. This study reports the first structure-activity relationships on potency and selectivity of several iminocyclitols (2-7) for the GUSs. Complex structures of Ruminococcus gnavus GUS with 2-7 explained how charge, conformation, and substituent of iminocyclitols affect their potency and selectivity. N1 of uronic isofagomine (2) made strong electrostatic interactions with two catalytic glutamates of GUSs, resulting in the most potent inhibition (Ki &gt;/= 11 nM). C6-propyl analogue of 2 (6) displayed 700-fold selectivity for opportunistic bacterial GUSs (Ki = 74 nM for E. coli GUS and 51.8 muM for RgGUS). In comparison with 2, there was 200-fold enhancement in the selectivity, which was attributed to differential interactions between the propyl group and loop 5 residues of the GUSs. The results provide useful insights to develop potent and selective inhibitors for undesired GUSs.

Substituent Position of Iminocyclitols Determines the Potency and Selectivity for Gut Microbial Xenobiotic-Reactivating Enzymes.,Dashnyam P, Lin HY, Chen CY, Gao S, Yeh LF, Hsieh WC, Tu Z, Lin CH J Med Chem. 2020 May 14;63(9):4617-4627. doi: 10.1021/acs.jmedchem.9b01918. Epub , 2020 Mar 9. PMID:32105467<ref>PMID:32105467</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6jz7" style="background-color:#fffaf0;"></div>

==See Also==
*[[Galactosidase 3D structures|Galactosidase 3D structures]]
*[[Glucuronisidase 3D structures|Glucuronisidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Dashnyam P]]
[[Category: Lin HY]]