3L6P

Crystal Structure of Dengue Virus 1 NS2B/NS3 protease


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.284 
  • R-Value Work: 0.239 
  • R-Value Observed: 0.242 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Serotype-specific structural differences in the protease-cofactor complexes of the dengue virus family.

Chandramouli, S.Joseph, J.S.Daudenarde, S.Gatchalian, J.Cornillez-Ty, C.Kuhn, P.

(2010) J Virol 84: 3059-3067

  • DOI: https://doi.org/10.1128/JVI.02044-09
  • Primary Citation of Related Structures:  
    3L6P, 3LKW

  • PubMed Abstract: 

    With an estimated 40% of the world population at risk, dengue poses a significant threat to human health, especially in tropical and subtropical regions. Preventative and curative efforts, such as vaccine development and drug discovery, face additional challenges due to the occurrence of four antigenically distinct serotypes of the causative dengue virus (DEN1 to -4). Complex immune responses resulting from repeat assaults by the different serotypes necessitate simultaneous targeting of all forms of the virus. One of the promising targets for drug development is the highly conserved two-component viral protease NS2B-NS3, which plays an essential role in viral replication by processing the viral precursor polyprotein into functional proteins. In this paper, we report the 2.1-A crystal structure of the DEN1 NS2B hydrophilic core (residues 49 to 95) in complex with the NS3 protease domain (residues 1 to 186) carrying an internal deletion in the N terminus (residues 11 to 20). While the overall folds within the protease core are similar to those of DEN2 and DEN4 proteases, the conformation of the cofactor NS2B is dramatically different from those of other flaviviral apoprotease structures. The differences are especially apparent within its C-terminal region, implicated in substrate binding. The structure reveals for the first time serotype-specific structural elements in the dengue virus family, with the reported alternate conformation resulting from a unique metal-binding site within the DEN1 sequence. We also report the identification of a 10-residue stretch within NS3pro that separates the substrate-binding function from the catalytic turnover rate of the enzyme. Implications for broad-spectrum drug discovery are discussed.


  • Organizational Affiliation

    Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
fusion protein of nonstructural protein 2B and nonstructural protein 3236Dengue virus 1 Singapore/S275/1990Dengue virus 1 Nauru/West Pac/1974
This entity is chimeric
Mutation(s): 0 
EC: 3.4.21.91 (PDB Primary Data), 3.6.1.15 (PDB Primary Data), 3.6.4.13 (PDB Primary Data), 2.1.1.56 (PDB Primary Data), 2.1.1.57 (PDB Primary Data), 2.7.7.48 (PDB Primary Data)
UniProt
Find proteins for P17763 (Dengue virus type 1 (strain Nauru/West Pac/1974))
Explore P17763 
Go to UniProtKB:  P17763
Find proteins for P33478 (Dengue virus type 1 (strain Singapore/S275/1990))
Explore P33478 
Go to UniProtKB:  P33478
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP17763P33478
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.284 
  • R-Value Work: 0.239 
  • R-Value Observed: 0.242 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.721α = 90
b = 60.848β = 90
c = 161.644γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-03-02
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-06-21
    Changes: Database references, Source and taxonomy, Structure summary
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description