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 4J02

Crystal structure of hcv ns5b polymerase in complex with [(1R)-5,8-DICHLORO-1-PROPYL-1,3,4,9-TETRAHYDROPYRANO[3,4-B]INDOL-1-YL]ACETIC ACID

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.195 

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 AnnotationsExpand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
1JE
Query on 1JE
Download Ideal Coordinates CCD File 
C [auth A],
F [auth B]		[(1R)-5,8-dichloro-1-propyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl]acetic acid
C16 H17 Cl2 N O3
DKHFCUNJXIAWGU-MRXNPFEDSA-N
SO4
Query on SO4
Download Ideal Coordinates CCD File 
D [auth A],
G [auth B]		SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
NA
Query on NA
Download Ideal Coordinates CCD File 
E [auth A],
H [auth B]		SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.195 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 105.76α = 90
b = 108.34β = 90
c = 133.06γ = 90
Software Package:
Software NamePurpose
MAR345dtbdata collection
CNSrefinement
CNXrefinement
HKL-2000data reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


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: 2024-10-30
    Changes: Data collection, Database references, Derived calculations, Structure summary