6U7I

Faecalibacterium prausnitzii Beta-glucuronidase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.183 

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This is version 1.3 of the entry. See complete history


Literature

Gut microbial beta-glucuronidases reactivate estrogens as components of the estrobolome that reactivate estrogens.

Ervin, S.M.Li, H.Lim, L.Roberts, L.R.Liang, X.Mani, S.Redinbo, M.R.

(2019) J Biol Chem 294: 18586-18599

  • DOI: https://doi.org/10.1074/jbc.RA119.010950
  • Primary Citation of Related Structures:  
    6U7I, 6U7J

  • PubMed Abstract: 

    Gut microbial β-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.


  • Organizational Affiliation

    Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-glucuronidase
A, B, C, D
597Faecalibacterium prausnitziiMutation(s): 0 
Gene Names: CGS54_08875
UniProt
Find proteins for A0A3F3JX71 (Faecalibacterium prausnitzii)
Explore A0A3F3JX71 
Go to UniProtKB:  A0A3F3JX71
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A3F3JX71
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.183 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 122.597α = 90
b = 129.055β = 90
c = 161.424γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
PHENIXphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Cancer Institute (NIH/NCI)United StatesCA22469

Revision History  (Full details and data files)

  • Version 1.0: 2019-10-30
    Type: Initial release
  • Version 1.1: 2019-12-04
    Changes: Author supporting evidence
  • Version 1.2: 2021-05-12
    Changes: Database references
  • Version 1.3: 2023-10-11
    Changes: Data collection, Database references, Refinement description