6T1Q

3C-like protease from Southampton norovirus.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.30 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.151 
  • R-Value Observed: 0.153 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

In crystallo-screening for discovery of human norovirus 3C-like protease inhibitors.

Guo, J.Douangamath, A.Song, W.Coker, A.R.Chan, A.W.E.Wood, S.P.Cooper, J.B.Resnick, E.London, N.Delft, F.V.

(2020) J Struct Biol X 4: 100031-100031

  • DOI: https://doi.org/10.1016/j.yjsbx.2020.100031
  • Primary Citation of Related Structures:  
    6T1Q, 6T2I, 6T2X, 6T3G, 6T49, 6T4E, 6T4S, 6T5D, 6T5R, 6T6W, 6T71, 6T82, 6T8R, 6T8T, 6TAL, 6TAW, 6TBO, 6TBP, 6TC1, 6TCF, 6TGL

  • PubMed Abstract: 

    Outbreaks of human epidemic nonbacterial gastroenteritis are mainly caused by noroviruses. Viral replication requires a 3C-like cysteine protease (3CL pro ) which processes the 200 kDa viral polyprotein into six functional proteins. The 3CL pro has attracted much interest due to its potential as a target for antiviral drugs. A system for growing high-quality crystals of native Southampton norovirus 3CL pro (SV3CP) has been established, allowing the ligand-free crystal structure to be determined to 1.3 Å in a tetrameric state. This also allowed crystal-based fragment screening to be performed with various compound libraries, ultimately to guide drug discovery for SV3CP. A total of 19 fragments were found to bind to the protease out of the 844 which were screened. Two of the hits were located at the active site of SV3CP and showed good inhibitory activity in kinetic assays. Another 5 were found at the enzyme's putative RNA-binding site and a further 11 were located in the symmetric central cavity of the tetramer.


  • Organizational Affiliation

    Division of Medicine, UCL, Gower Street, London WC1E 6BT, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Genome polyprotein172Southampton virus (serotype 3)Mutation(s): 0 
Gene Names: ORF1
EC: 3.6.1.15 (PDB Primary Data), 3.4.22.66 (PDB Primary Data), 2.7.7.48 (PDB Primary Data)
UniProt
Find proteins for Q04544 (Southampton virus (strain GI/Human/United Kingdom/Southampton/1991))
Explore Q04544 
Go to UniProtKB:  Q04544
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ04544
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Genome polyprotein169Southampton virus (serotype 3)Mutation(s): 0 
Gene Names: ORF1
EC: 3.6.1.15 (PDB Primary Data), 3.4.22.66 (PDB Primary Data), 2.7.7.48 (PDB Primary Data)
UniProt
Find proteins for Q04544 (Southampton virus (strain GI/Human/United Kingdom/Southampton/1991))
Explore Q04544 
Go to UniProtKB:  Q04544
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ04544
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.30 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.151 
  • R-Value Observed: 0.153 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.133α = 90
b = 89.359β = 96.48
c = 61.581γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
xia2data reduction
Aimlessdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2020-08-19
    Type: Initial release
  • Version 1.1: 2024-01-24
    Changes: Data collection, Database references, Refinement description