4IZ0 | pdb_00004iz0

Crystal structure of HCV NS5B polymerase in complex with 2,4,5-trichloro-N-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.22 Å
  • R-Value Free: 
    0.275 (Depositor), 0.260 (DCC) 
  • R-Value Work: 
    0.253 (Depositor), 0.240 (DCC) 

Starting Model: experimental
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Ligand Structure Quality Assessment 

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This is version 1.3 of the entry. See complete history. 


Literature

Discovery of a novel series of non-nucleoside thumb pocket 2 HCV NS5B polymerase inhibitors.

Stammers, T.A., Coulombe, R., Rancourt, J., Thavonekham, B., Fazal, G., Goulet, S., Jakalian, A., Wernic, D., Tsantrizos, Y., Poupart, M.A., Bos, M., McKercher, G., Thauvette, L., Kukolj, G., Beaulieu, P.L.

(2013) Bioorg Med Chem Lett 23: 2585-2589

  • DOI: https://doi.org/10.1016/j.bmcl.2013.02.110
  • Primary Citation of Related Structures:  
    4IZ0, 4J02, 4J04, 4J06, 4J08, 4J0A

  • PubMed Abstract: 

    A novel series of non-nucleoside thumb pocket 2 HCV NS5B polymerase inhibitors were derived from a fragment-based approach using information from X-ray crystallographic analysis of NS5B-inhibitor complexes and iterative rounds of parallel synthesis. Structure-based drug design strategies led to the discovery of potent sub-micromolar inhibitors 11a-c and 12a-c from a weak-binding fragment-like structure 1 as a starting point.

    • Organizational Affiliation: 

    Department of Chemistry, Boehringer Ingelheim (Canada) Ltd, Research and Development, 2100 rue Cunard, Laval, Québec, Canada H7S 2G5. timothy.stammers@boehringer-ingelheim.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA-directed RNA polymerase
A, B
576Hepatitis C virus isolate HC-J4Mutation(s): 0 
Gene Names: NS5B
EC: 2.7.7.48
UniProt
Find proteins for O92972 (Hepatitis C virus genotype 1b (strain HC-J4))
Explore O92972 
Go to UniProtKB:  O92972
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO92972
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.22 Å
  • R-Value Free:  0.275 (Depositor), 0.260 (DCC) 
  • R-Value Work:  0.253 (Depositor), 0.240 (DCC) 
Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 105.71α = 90
b = 107.85β = 90
c = 133.95γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted 2BIClick on this verticalbar to view details

View more in-depth experimental data
Entry History 

Deposition Data

  • Released Date: 2013-04-17 
    • Deposition Author(s): Coulombe, R.

Revision History  (Full details and data files)

  • Version 1.0: 2013-04-17
    Type: Initial release
  • Version 1.1: 2013-05-01
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.3: 2024-10-30
    Changes: Structure summary