3OSY

Human enterovirus 71 3C protease


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.99 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.209 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Crystal Structure of Human Enterovirus 71 3C Protease.

Cui, S.Wang, J.Fan, T.Qin, B.Guo, L.Lei, X.Wang, J.Wang, M.Jin, Q.

(2011) J Mol Biol 408: 449-461

  • DOI: https://doi.org/10.1016/j.jmb.2011.03.007
  • Primary Citation of Related Structures:  
    3OSY

  • PubMed Abstract: 

    Human enterovirus 71 (EV71) is the major pathogen that causes hand, foot and mouth disease that particularly affects young children. Growing hand, foot and mouth disease outbreaks were observed worldwide in recent years and caused devastating losses both economically and politically. However, vaccines or effective drugs are unavailable to date. The genome of EV71 consists of a positive sense, single-stranded RNA of ∼7400 bp, encoding a large precursor polyprotein that requires proteolytic processing to generate mature viral proteins. The proteolytic processing mainly depends on EV71 3C protease (3C(pro)) that possesses both proteolysis and RNA binding activities, which enable the protease to perform multiple tasks in viral replication and pathogen-host interactions. The central roles played by EV71 3C(pro) make it an appealing target for antiviral drug development. We determined the first crystal structure of EV71 3C(pro) and analyzed its enzymatic activity. The crystal structure shows that EV71 3C(pro) has a typical chymotrypsin-like fold that is common in picornaviral 3C(pro). Strikingly, we found an important surface loop, also denoted as β-ribbon, which adopts a novel open conformation in EV71 3C(pro). We identified two important residues located at the base of the β-ribbon, Gly123 and His133, which form hinges that govern the intrinsic flexibility of the ribbon. Structure-guided mutagenesis studies revealed that the hinge residues are important to EV71 3C(pro) proteolytic activities. In summary, our work provides the first structural insight into EV71 3C(pro), including a mobile β-ribbon, which is relevant to the proteolytic mechanism. Our data also provides a framework for structure-guided inhibitor design against EV71 3C(pro).


  • Organizational Affiliation

    State Key Laboratory for Molecular Virology and Genetic Engineering, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People's Republic of China. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
3C protease
A, B, C, D, E
204Enterovirus A71Mutation(s): 0 
Gene Names: 3C
UniProt
Find proteins for B8YLV9 (Human enterovirus 71)
Explore B8YLV9 
Go to UniProtKB:  B8YLV9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupB8YLV9
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.99 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.209 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 54.288α = 90
b = 75.121β = 90.11
c = 125.153γ = 90
Software Package:
Software NamePurpose
RemDAqdata collection
PHASERphasing
PHENIXrefinement
XDSdata reduction
XDSdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-03-23
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Refinement description