6d7j
From Proteopedia
(Difference between revisions)
| Line 3: | Line 3: | ||
<StructureSection load='6d7j' size='340' side='right'caption='[[6d7j]], [[Resolution|resolution]] 2.24Å' scene=''> | <StructureSection load='6d7j' size='340' side='right'caption='[[6d7j]], [[Resolution|resolution]] 2.24Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6d7j]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Parabacteroides_merdae_cl03t12c32 Parabacteroides merdae cl03t12c32]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D7J OCA]. For a <b>guided tour on the structure components</b> use [http:// | + | <table><tr><td colspan='2'>[[6d7j]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Parabacteroides_merdae_cl03t12c32 Parabacteroides merdae cl03t12c32]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D7J OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6D7J FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PRO:PROLINE'>PRO</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PRO:PROLINE'>PRO</scene></td></tr> |
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HMPREF1060_00403 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=999420 Parabacteroides merdae CL03T12C32])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HMPREF1060_00403 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=999420 Parabacteroides merdae CL03T12C32])</td></tr> | ||
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6d7j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d7j OCA], [http://pdbe.org/6d7j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d7j RCSB], [http://www.ebi.ac.uk/pdbsum/6d7j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d7j ProSAT]</span></td></tr> |
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Gut microbial beta-glucuronidase (GUS) enzymes have been suggested to be involved in the estrobolome, the collection of microbial reactions involving estrogens. Furthermore, bacterial GUS enzymes within the gastrointestinal tract have been postulated to be a contributing factor in hormone-driven cancers. However, to date, there has been no experimental evidence to support these hypotheses. Here we provide the first in vitro analysis of the ability of 35 human gut microbial GUS enzymes to reactivate two distinct estrogen glucuronides, estrone-3-glucuronide and estradiol-17-glucuronide, to estrone and estradiol, respectively. We show that certain members within the Loop 1, mini-Loop 1, and FMN-binding classes of gut microbial GUS enzymes can reactivate estrogens from their inactive glucuronides. We provide molecular details of key interactions that facilitate these catalytic processes and present the structures of two novel human gut microbial GUS enzymes related to the estrobolome. Further, we demonstrate that estrogen reactivation by Loop 1 bacterial GUS enzymes can be inhibited both in purified enzymes and in fecal preparations of mixed murine fecal microbiota. Finally, however, despite these in vitro and ex vivo data, we show that a Loop 1 GUS-specific inhibitor is not capable of reducing the development of tumors in the PyMT mouse model of breast cancer. These findings validate that gut microbial GUS enzymes participate in the estrobolome but also suggest that the estrobolome is a multidimensional set of processes on-going within the mammalian gastrointestinal tract that likely involves many enzymes, including several distinct types of GUS proteins. | ||
| + | |||
| + | Gut microbial beta-glucuronidases reactivate estrogens as components of the estrobolome that reactivate estrogens.,Ervin SM, Li H, Lim L, Roberts LR, Liang X, Mani S, Redinbo MR J Biol Chem. 2019 Dec 6;294(49):18586-18599. doi: 10.1074/jbc.RA119.010950. Epub , 2019 Oct 21. PMID:31636122<ref>PMID:31636122</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6d7j" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Glucuronisidase 3D structures|Glucuronisidase 3D structures]] | *[[Glucuronisidase 3D structures|Glucuronisidase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 05:42, 13 May 2020
The Crystal Structure of Parabacteroides merdae Beta-Glucuronidase (GUS) with Glycerol in Active-Site
| |||||||||||
