7GP2

PanDDA analysis group deposition -- Crystal Structure of Enterovirus D68 3C Protease in complex with Z425757818


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.31 Å
  • R-Value Free: 0.202 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.186 

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

Crystallographic Fragment Screen of Coxsackievirus A16 2A Protease identifies new opportunities for the development of broad-spectrum anti-enterovirals.

Lithgo, R.M.Tomlinson, C.W.E.Fairhead, M.Winokan, M.Thompson, W.Wild, C.Aschenbrenner, J.C.Balcomb, B.H.Marples, P.G.Chandran, A.V.Golding, M.Koekemoer, L.Williams, E.P.Wang, S.Ni, X.MacLean, E.Giroud, C.Godoy, A.S.Xavier, M.A.Walsh, M.Fearon, D.von Delft, F.

(2024) bioRxiv 

  • DOI: https://doi.org/10.1101/2024.04.29.591684
  • Primary Citation of Related Structures:  
    7GNV, 7GNW, 7GNX, 7GNY, 7GNZ, 7GO0, 7GO1, 7GO2, 7GO3, 7GO4, 7GO5, 7GO6, 7GO7, 7GO8, 7GO9, 7GOA, 7GOB, 7GOC, 7GOD, 7GOE, 7GOF, 7GOG, 7GOH, 7GOI, 7GOJ, 7GOK, 7GOL, 7GOM, 7GON, 7GOO, 7GOP, 7GOQ, 7GOR, 7GOS, 7GOT, 7GOU, 7GOV, 7GOW, 7GOX, 7GOY, 7GOZ, 7GP0, 7GP1, 7GP2, 7GP3, 7GP4, 7GP5, 7GP6, 7GP7, 7GP8

  • PubMed Abstract: 

    Enteroviruses are the causative agents of paediatric hand-foot-and-mouth disease, and a target for pandemic preparedness due to the risk of higher order complications in a large-scale outbreak. The 2A protease of these viruses is responsible for the self-cleavage of the poly protein, allowing for correct folding and assembly of capsid proteins in the final stages of viral replication. These 2A proteases are highly conserved between Enterovirus species, such as Enterovirus A71 and Coxsackievirus A16 . Inhibition of the 2A protease deranges capsid folding and assembly, preventing formation of mature virions in host cells and making the protease a valuable target for antiviral activity. Herein, we describe a crystallographic fragment screening campaign that identified 75 fragments which bind to the 2A protease including 38 unique compounds shown to bind within the active site. These fragments reveal a path for the development of non-peptidomimetic inhibitors of the 2A protease with broad-spectrum anti-enteroviral activity.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protease 3C
A, B
182enterovirus D68Mutation(s): 0 
EC: 3.4.22.28
UniProt
Find proteins for Q68T42 (Human enterovirus D68)
Explore Q68T42 
Go to UniProtKB:  Q68T42
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ68T42
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.31 Å
  • R-Value Free: 0.202 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.186 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.772α = 90
b = 62.308β = 90
c = 147.2γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
Aimlessdata scaling
PHASERphasing
XDSdata reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

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

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesU19AI171399

Revision History  (Full details and data files)

  • Version 1.0: 2023-11-29
    Type: Initial release
  • Version 1.1: 2024-09-11
    Changes: Author supporting evidence
  • Version 1.2: 2024-10-16
    Changes: Database references, Structure summary