5EU8

Structure of FIPV main protease in complex with dual inhibitors


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.213 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Crystal Structure of Feline Infectious Peritonitis Virus Main Protease in Complex with Synergetic Dual Inhibitors

Wang, F.Chen, C.Liu, X.Yang, K.Xu, X.Yang, H.

(2015) J Virol 90: 1910-1917

  • DOI: https://doi.org/10.1128/JVI.02685-15
  • Primary Citation of Related Structures:  
    5EU8

  • PubMed Abstract: 

    Coronaviruses (CoVs) can cause highly prevalent diseases in humans and animals. Feline infectious peritonitis virus (FIPV) belongs to the genus Alphacoronavirus, resulting in a lethal systemic granulomatous disease called feline infectious peritonitis (FIP), which is one of the most important fatal infectious diseases of cats worldwide. No specific vaccines or drugs have been approved to treat FIP. CoV main proteases (M(pro)s) play a pivotal role in viral transcription and replication, making them an ideal target for drug development. Here, we report the crystal structure of FIPV M(pro) in complex with dual inhibitors, a zinc ion and a Michael acceptor. The complex structure elaborates a unique mechanism of two distinct inhibitors synergizing to inactivate the protease, providing a structural basis to design novel antivirals and suggesting the potential to take advantage of zinc as an adjunct therapy against CoV-associated diseases.


  • Organizational Affiliation

    School of Life Sciences, Tianjin University, Tianjin, People's Republic of China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
main protease307Feline infectious peritonitis virusMutation(s): 0 
Gene Names: 1bORF1a
UniProt
Find proteins for Q98VG9 (Feline coronavirus (strain FIPV WSU-79/1146))
Explore Q98VG9 
Go to UniProtKB:  Q98VG9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ98VG9
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
N-[(5-METHYLISOXAZOL-3-YL)CARBONYL]ALANYL-L-VALYL-N~1~-((1R,2Z)-4-(BENZYLOXY)-4-OXO-1-{[(3R)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-L-LEUCINAMIDE6synthetic constructMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.213 
  • Space Group: I 4 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 112.261α = 90
b = 112.261β = 90
c = 102.102γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
SCALEPACKdata reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Key Basic Research Program of China (973 program)China2015CB859800
National Natural Science Foundation of ChinaChina31300150
Tianjin Marine Science and Technology ProgramChinaKJXH2014-16

Revision History  (Full details and data files)

  • Version 1.0: 2015-12-30
    Type: Initial release
  • Version 1.1: 2016-02-10
    Changes: Database references
  • Version 1.2: 2023-11-08
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 2.0: 2023-11-15
    Changes: Atomic model, Data collection, Derived calculations