6T4C

Bovine enterovirus F3 in complex with glutathione


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.205 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Glutathione facilitates enterovirus assembly by binding at a druggable pocket.

Duyvesteyn, H.M.E.Ren, J.Walter, T.S.Fry, E.E.Stuart, D.I.

(2020) Commun Biol 3: 9-9

  • DOI: https://doi.org/10.1038/s42003-019-0722-x
  • Primary Citation of Related Structures:  
    6T40, 6T48, 6T4C

  • PubMed Abstract: 

    Enteroviruses cause a range of human and animal diseases, some life-threatening, but there remain no licenced anti-enterovirus drugs. However, a benzene-sulfonamide derivative and related compounds have been shown recently to block infection of a range of enteroviruses by binding the capsid at a positively-charged surface depression conserved across many enteroviruses. It has also been established that glutathione is essential for the assembly of many enteroviruses, interacting with the capsid proteins to facilitate the formation of the pentameric assembly intermediate, although the mechanism is unknown. Here we show, by high resolution structure analyses of enterovirus F3, that reduced glutathione binds to the same interprotomer pocket as the benzene-sulfonamide derivative. Bound glutathione makes strong interactions with adjacent protomers, thereby explaining the underlying biological role of this druggable binding pocket and delineating the pharmacophore for potential antivirals.


  • Organizational Affiliation

    1Division of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford OX3 7BN UK.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
VP1275Enterovirus FMutation(s): 0 
EC: 3.4.22.29 (PDB Primary Data), 3.6.1.15 (PDB Primary Data), 3.4.22.28 (PDB Primary Data), 2.7.7.48 (PDB Primary Data)
UniProt
Find proteins for Q2LKZ0 (Enterovirus F)
Explore Q2LKZ0 
Go to UniProtKB:  Q2LKZ0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ2LKZ0
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
VP2244Enterovirus FMutation(s): 0 
EC: 3.4.22.29 (PDB Primary Data), 3.6.1.15 (PDB Primary Data), 3.4.22.28 (PDB Primary Data), 2.7.7.48 (PDB Primary Data)
UniProt
Find proteins for Q2LKZ0 (Enterovirus F)
Explore Q2LKZ0 
Go to UniProtKB:  Q2LKZ0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ2LKZ0
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
VP3243Enterovirus FMutation(s): 0 
EC: 3.4.22.29 (PDB Primary Data), 3.6.1.15 (PDB Primary Data), 3.4.22.28 (PDB Primary Data), 2.7.7.48 (PDB Primary Data)
UniProt
Find proteins for Q2LKZ0 (Enterovirus F)
Explore Q2LKZ0 
Go to UniProtKB:  Q2LKZ0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ2LKZ0
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
VP471Enterovirus FMutation(s): 0 
EC: 3.4.22.29 (PDB Primary Data), 3.6.1.15 (PDB Primary Data), 3.4.22.28 (PDB Primary Data), 2.7.7.48 (PDB Primary Data)
UniProt
Find proteins for Q2LKZ0 (Enterovirus F)
Explore Q2LKZ0 
Go to UniProtKB:  Q2LKZ0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ2LKZ0
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GSH (Subject of Investigation/LOI)
Query on GSH

Download Ideal Coordinates CCD File 
N [auth C]GLUTATHIONE
C10 H17 N3 O6 S
RWSXRVCMGQZWBV-WDSKDSINSA-N
STE
Query on STE

Download Ideal Coordinates CCD File 
E [auth A]STEARIC ACID
C18 H36 O2
QIQXTHQIDYTFRH-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
F [auth A]
H [auth A]
L [auth B]
O [auth C]
P [auth C]
F [auth A],
H [auth A],
L [auth B],
O [auth C],
P [auth C],
Q [auth C]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
G [auth A],
I [auth A]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
K
Query on K

Download Ideal Coordinates CCD File 
J [auth A],
K [auth A],
M [auth B],
R [auth C]
POTASSIUM ION
K
NPYPAHLBTDXSSS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.205 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 342.75α = 90
b = 348.16β = 90
c = 351.42γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DIALSdata reduction
Aimlessdata scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Medical Research Council (United Kingdom)United KingdomMR/N00065X/1
Wellcome TrustUnited Kingdom101122/Z/13/Z
Wellcome TrustUnited KingdomALR00750

Revision History  (Full details and data files)

  • Version 1.0: 2020-01-15
    Type: Initial release
  • Version 1.1: 2021-09-01
    Changes: Database references, Derived calculations
  • Version 1.2: 2022-12-21
    Changes: Refinement description
  • Version 1.3: 2023-03-15
    Changes: Other, Refinement description
  • Version 1.4: 2024-02-07
    Changes: Data collection, Refinement description