7ODM

AmGSTF1 Y118S variant


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.188 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

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This is version 1.2 of the entry. See complete history


Literature

Flavonoid-based inhibitors of the Phi-class glutathione transferase from black-grass to combat multiple herbicide resistance.

Schwarz, M.Eno, R.F.M.Freitag-Pohl, S.Coxon, C.R.Straker, H.E.Wortley, D.J.Hughes, D.J.Mitchell, G.Moore, J.Cummins, I.Onkokesung, N.Brazier-Hicks, M.Edwards, R.Pohl, E.Steel, P.G.

(2021) Org Biomol Chem 19: 9211-9222

  • DOI: https://doi.org/10.1039/d1ob01802g
  • Primary Citation of Related Structures:  
    6TO3, 7OBO, 7ODM

  • PubMed Abstract: 

    The evolution and growth of multiple-herbicide resistance (MHR) in grass weeds continues to threaten global cereal production. While various processes can contribute to resistance, earlier work has identified the phi class glutathione- S -transferase ( Am GSTF1) as a functional biomarker of MHR in black-grass ( Alopecurus myosuroides ). This study provides further insights into the role of Am GSTF1 in MHR using a combination of chemical and structural biology. Crystal structures of wild-type Am GSTF1, together with two specifically designed variants that allowed the co-crystal structure determination with glutathione and a glutathione adduct of the Am GSTF1 inhibitor 4-chloro-7-nitro-benzofurazan (NBD-Cl) were obtained. These studies demonstrated that the inhibitory activity of NBD-Cl was associated with the occlusion of the active site and the impediment of substrate binding. A search for other selective inhibitors of Am GSTF1, using ligand-fishing experiments, identified a number of flavonoids as potential ligands. Subsequent experiments using black-grass extracts discovered a specific flavonoid as a natural ligand of the recombinant enzyme. A series of related synthetic flavonoids was prepared and their binding to Am GSTF1 was investigated showing a high affinity for derivatives bearing a O -5-decyl-α-carboxylate. Molecular modelling based on high-resolution crystal structures allowed a binding pose to be defined which explained flavonoid binding specificity. Crucially, high binding affinity was linked to a reversal of the herbicide resistance phenotype in MHR black-grass. Collectively, these results present a nature-inspired new lead for the development of herbicide synergists to counteract MHR in weeds.


  • Organizational Affiliation

    Department of Chemistry, University of Durham, Science Laboratories, South Road, Durham, DH1 3LE, UK. p.g.steel@durham.ac.uk.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glutathione transferaseA [auth AAA]219Alopecurus myosuroidesMutation(s): 1 
Gene Names: GST2c
EC: 2.5.1.18
UniProt
Find proteins for Q9ZS17 (Alopecurus myosuroides)
Explore Q9ZS17 
Go to UniProtKB:  Q9ZS17
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9ZS17
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
VDW (Subject of Investigation/LOI)
Query on VDW

Download Ideal Coordinates CCD File 
B [auth AAA][(2~{S})-5-[[(2~{R})-1-(2-hydroxy-2-oxoethylamino)-1-oxidanylidene-3-sulfanyl-propan-2-yl]amino]-1-oxidanyl-1,5-bis(oxidanylidene)pentan-2-yl]azanium
C10 H18 N3 O6 S
RWSXRVCMGQZWBV-WDSKDSINSA-O
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.188 
  • Space Group: I 41 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 112.611α = 90
b = 112.611β = 90
c = 103.646γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
xia2data reduction
xia2data scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted VDWClick on this verticalbar to view details

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Biotechnology and Biological Sciences Research Council (BBSRC)United KingdomBB/G006474/2

Revision History  (Full details and data files)

  • Version 1.0: 2022-04-20
    Type: Initial release
  • Version 1.1: 2022-04-27
    Changes: Database references
  • Version 1.2: 2024-01-31
    Changes: Data collection, Derived calculations, Refinement description