6DIZ

EV-A71 strain 11316 complexed with tryptophan dendrimer MADAL_0385


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.59 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Viral engagement with host (co-)receptors blocked by a novel class of tryptophan dendrimers that targets the 5-fold-axis of the enterovirus-A71 capsid.

Sun, L.Lee, H.Thibaut, H.J.Lanko, K.Rivero-Buceta, E.Bator, C.Martinez-Gualda, B.Dallmeier, K.Delang, L.Leyssen, P.Gago, F.San-Felix, A.Hafenstein, S.Mirabelli, C.Neyts, J.

(2019) PLoS Pathog 15: e1007760-e1007760

  • DOI: https://doi.org/10.1371/journal.ppat.1007760
  • Primary Citation of Related Structures:  
    6DIZ

  • PubMed Abstract: 

    Enterovirus A71 (EV-A71) is a non-polio neurotropic enterovirus with pandemic potential. There are no antiviral agents approved to prevent or treat EV-A71 infections. We here report on the molecular mechanism by which a novel class of tryptophan dendrimers inhibits (at low nanomolar to high picomolar concentration) EV-A71 replication in vitro. A lead compound in the series (MADAL385) prevents binding and internalization of the virus but does not, unlike classical capsid binders, stabilize the particle. By means of resistance selection, reverse genetics and cryo-EM, we map the binding region of MADAL385 to the 5-fold vertex of the viral capsid and demonstrate that a single molecule binds to each vertex. By interacting with this region, MADAL385 prevents the interaction of the virus with its cellular receptors PSGL1 and heparan sulfate, thereby blocking the attachment of EV-A71 to the host cells.


  • Organizational Affiliation

    KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
VP1297Enterovirus A71Mutation(s): 0 
UniProt
Find proteins for I6W7A3 (Human enterovirus 71)
Explore I6W7A3 
Go to UniProtKB:  I6W7A3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupI6W7A3
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
VP2245Enterovirus A71Mutation(s): 0 
UniProt
Find proteins for I6W7A3 (Human enterovirus 71)
Explore I6W7A3 
Go to UniProtKB:  I6W7A3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupI6W7A3
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
VP3242Enterovirus A71Mutation(s): 0 
UniProt
Find proteins for I6W7A3 (Human enterovirus 71)
Explore I6W7A3 
Go to UniProtKB:  I6W7A3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupI6W7A3
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
VP478Enterovirus A71Mutation(s): 0 
UniProt
Find proteins for I6W7A3 (Human enterovirus 71)
Explore I6W7A3 
Go to UniProtKB:  I6W7A3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupI6W7A3
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SPH
Query on SPH

Download Ideal Coordinates CCD File 
E [auth A]SPHINGOSINE
C18 H37 N O2
WWUZIQQURGPMPG-MSOLQXFVSA-N
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.59 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
European Regional Development Fund--

Revision History  (Full details and data files)

  • Version 1.0: 2019-04-24
    Type: Initial release
  • Version 1.1: 2019-05-22
    Changes: Data collection, Database references
  • Version 1.2: 2019-12-18
    Changes: Other
  • Version 1.3: 2024-03-13
    Changes: Data collection, Database references, Derived calculations