5IDK

Crystal structure of West Nile Virus NS2B-NS3 protease in complex with a capped dipeptide boronate inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.186 
  • R-Value Work: 0.159 
  • R-Value Observed: 0.161 

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Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Peptide-Boronic Acid Inhibitors of Flaviviral Proteases: Medicinal Chemistry and Structural Biology.

Nitsche, C.Zhang, L.Weigel, L.F.Schilz, J.Graf, D.Bartenschlager, R.Hilgenfeld, R.Klein, C.D.

(2017) J Med Chem 60: 511-516

  • DOI: https://doi.org/10.1021/acs.jmedchem.6b01021
  • Primary Citation of Related Structures:  
    5IDK

  • PubMed Abstract: 

    A thousand-fold affinity gain is achieved by introduction of a C-terminal boronic acid moiety into dipeptidic inhibitors of the Zika, West Nile, and dengue virus proteases. The resulting compounds have K i values in the two-digit nanomolar range, are not cytotoxic, and inhibit virus replication. Structure-activity relationships and a high resolution X-ray cocrystal structure with West Nile virus protease provide a basis for the design of optimized covalent-reversible inhibitors aimed at emerging flaviviral pathogens.


  • Organizational Affiliation

    Medicinal Chemistry, IPMB, Heidelberg University , INF-364, 69120 Heidelberg, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Genome polyprotein,SERINE PROTEASE SUBUNIT NS2B, SERINE PROTEASE NS3
A, B, C
230West Nile virusMutation(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 P06935 (West Nile virus)
Explore P06935 
Go to UniProtKB:  P06935
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP06935
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.186 
  • R-Value Work: 0.159 
  • R-Value Observed: 0.161 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 36.42α = 90
b = 96.965β = 90
c = 187.856γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
German Research FoundationGermanyKL-1356/3-1

Revision History  (Full details and data files)

  • Version 1.0: 2016-12-14
    Type: Initial release
  • Version 1.1: 2016-12-28
    Changes: Database references
  • Version 1.2: 2017-01-25
    Changes: Database references
  • Version 1.3: 2017-07-05
    Changes: Refinement description
  • Version 1.4: 2017-09-06
    Changes: Author supporting evidence
  • Version 1.5: 2024-01-10
    Changes: Advisory, Data collection, Database references, Refinement description