6D8K

Bacteroides multiple species beta-glucuronidase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Three structurally and functionally distinct beta-glucuronidases from the human gut microbeBacteroides uniformis.

Pellock, S.J.Walton, W.G.Biernat, K.A.Torres-Rivera, D.Creekmore, B.C.Xu, Y.Liu, J.Tripathy, A.Stewart, L.J.Redinbo, M.R.

(2018) J Biol Chem 293: 18559-18573

  • DOI: https://doi.org/10.1074/jbc.RA118.005414
  • Primary Citation of Related Structures:  
    6D1N, 6D1P, 6D41, 6D50, 6D6W, 6D7F, 6D89, 6D8G, 6D8K

  • PubMed Abstract: 

    The glycoside hydrolases encoded by the human gut microbiome play an integral role in processing a variety of exogenous and endogenous glycoconjugates. Here we present three structurally and functionally distinct β-glucuronidase (GUS) glycoside hydrolases from a single human gut commensal microbe, Bacteroides uniformis We show using nine crystal structures, biochemical, and biophysical data that whereas these three proteins share similar overall folds, they exhibit different structural features that create three structurally and functionally unique enzyme active sites. Notably, quaternary structure plays an important role in creating distinct active site features that are hard to predict via structural modeling methods. The enzymes display differential processing capabilities toward glucuronic acid-containing polysaccharides and SN-38-glucuronide, a metabolite of the cancer drug irinotecan. We also demonstrate that GUS-specific and nonselective inhibitors exhibit varying potencies toward each enzyme. Together, these data highlight the diversity of GUS enzymes within a single Bacteroides gut commensal and advance our understanding of how structural details impact the specific roles microbial enzymes play in processing drug-glucuronide and glycan substrates.


  • Organizational Affiliation

    From the Departments of Chemistry.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glycosyl hydrolase family 2, sugar binding domain protein
A, B, C, D
597Bacteroides ovatusMutation(s): 0 
Gene Names: HMPREF2532_04191
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 
  • Space Group: I 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 213.464α = 90
b = 213.464β = 90
c = 112.607γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Cancer Institute (NIH/NCI)United StatesCA098468
National Institutes of Health/National Cancer Institute (NIH/NCI)United StatesCA207416

Revision History  (Full details and data files)

  • Version 1.0: 2018-10-17
    Type: Initial release
  • Version 1.1: 2018-10-24
    Changes: Data collection, Database references
  • Version 1.2: 2018-12-19
    Changes: Data collection, Database references
  • Version 1.3: 2019-12-04
    Changes: Author supporting evidence
  • Version 1.4: 2024-03-13
    Changes: Data collection, Database references