4J08

Crystal structure of hcv ns5b polymerase in complex with 2-{[(4-METHYLPHENYL)SULFONYL]AMINO}-5-PHENOXYBENZOIC ACID


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.225 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 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
Genome polyprotein
A, B
576Hepatitis C virus isolate HC-J4Mutation(s): 0 
Gene Names: NS5B
EC: 3.4.22 (PDB Primary Data), 3.4.21.98 (PDB Primary Data), 3.6.1.15 (PDB Primary Data), 3.6.4.13 (PDB Primary Data), 2.7.7.48 (PDB Primary Data)
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
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
1JH
Query on 1JH

Download Ideal Coordinates CCD File 
C [auth A]2-{[(4-methylphenyl)sulfonyl]amino}-5-phenoxybenzoic acid
C20 H17 N O5 S
KFQWZEYUSVKRBI-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
1JH PDBBind:  4J08 IC50: 220 (nM) from 1 assay(s)
Binding MOAD:  4J08 IC50: 220 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.225 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 106.83α = 90
b = 107.68β = 90
c = 135.09γ = 90
Software Package:
Software NamePurpose
CNXrefinement
HKL-2000data reduction
SCALEPACKdata scaling
CNXphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


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