6ed2: Difference between revisions
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==Faecalibacterium prausnitzii beta-glucuronidase== | |||
<StructureSection load='6ed2' size='340' side='right' caption='[[6ed2]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6ed2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ED2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ED2 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6ed2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ed2 OCA], [http://pdbe.org/6ed2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ed2 RCSB], [http://www.ebi.ac.uk/pdbsum/6ed2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ed2 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Bacterial beta-glucuronidase (GUS) enzymes cause drug toxicity by reversing Phase II glucuronidation in the gastrointestinal tract. While many human gut microbial GUS enzymes have been examined with model glucuronide substrates like p-nitrophenol-beta-D-glucuronide (pNPG), the GUS orthologs that are most efficient at processing drug-glucuronides remain unclear. Here we present the crystal structures of GUS enzymes from human gut commensals Lactobacillus rhamnosus, Ruminococcus gnavus, and Faecalibacterium prausnitzii that possess an active site loop (Loop 1; L1) analogous to that found in E. coli GUS, which processes drug substrates. We also resolve the structure of the No Loop GUS from Bacteroides dorei. We then compare the pNPG and diclofenac glucuronide processing abilities of a panel of twelve structurally diverse GUS proteins, and find that the new L1 GUS enzymes presented here process small glucuronide substrates inefficiently compared to previously characterized L1 GUS enzymes like E. coli GUS. We further demonstrate that our GUS inhibitors, which are effective against some L1 enzymes, are not potent towards all. Our findings pinpoint active site structural features necessary for the processing of drug-glucuronide substrates and the inhibition of such processing. | |||
Structure, function, and inhibition of drug reactivating human gut microbial beta-glucuronidases.,Biernat KA, Pellock SJ, Bhatt AP, Bivins MM, Walton WG, Tran BNT, Wei L, Snider MC, Cesmat AP, Tripathy A, Erie DA, Redinbo MR Sci Rep. 2019 Jan 29;9(1):825. doi: 10.1038/s41598-018-36069-w. PMID:30696850<ref>PMID:30696850</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6ed2" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Biernat, K A]] | |||
[[Category: Pellock, S J]] | |||
[[Category: Redinbo, M R]] | |||
[[Category: Glycosyl hydrolase]] | |||
[[Category: Hydrolase]] | |||
Revision as of 12:28, 13 February 2019
Faecalibacterium prausnitzii beta-glucuronidaseFaecalibacterium prausnitzii beta-glucuronidase
Structural highlights
Publication Abstract from PubMedBacterial beta-glucuronidase (GUS) enzymes cause drug toxicity by reversing Phase II glucuronidation in the gastrointestinal tract. While many human gut microbial GUS enzymes have been examined with model glucuronide substrates like p-nitrophenol-beta-D-glucuronide (pNPG), the GUS orthologs that are most efficient at processing drug-glucuronides remain unclear. Here we present the crystal structures of GUS enzymes from human gut commensals Lactobacillus rhamnosus, Ruminococcus gnavus, and Faecalibacterium prausnitzii that possess an active site loop (Loop 1; L1) analogous to that found in E. coli GUS, which processes drug substrates. We also resolve the structure of the No Loop GUS from Bacteroides dorei. We then compare the pNPG and diclofenac glucuronide processing abilities of a panel of twelve structurally diverse GUS proteins, and find that the new L1 GUS enzymes presented here process small glucuronide substrates inefficiently compared to previously characterized L1 GUS enzymes like E. coli GUS. We further demonstrate that our GUS inhibitors, which are effective against some L1 enzymes, are not potent towards all. Our findings pinpoint active site structural features necessary for the processing of drug-glucuronide substrates and the inhibition of such processing. Structure, function, and inhibition of drug reactivating human gut microbial beta-glucuronidases.,Biernat KA, Pellock SJ, Bhatt AP, Bivins MM, Walton WG, Tran BNT, Wei L, Snider MC, Cesmat AP, Tripathy A, Erie DA, Redinbo MR Sci Rep. 2019 Jan 29;9(1):825. doi: 10.1038/s41598-018-36069-w. PMID:30696850[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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