3GOL

HCV NS5b polymerase in complex with 1,5 benzodiazepine inhibitor (R)-11d


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.85 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.191 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

1,5-Benzodiazepine inhibitors of HCV NS5B polymerase.

McGowan, D.Nyanguile, O.Cummings, M.D.Vendeville, S.Vandyck, K.Van den Broeck, W.Boutton, C.W.De Bondt, H.Quirynen, L.Amssoms, K.Bonfanti, J.F.Last, S.Rombauts, K.Tahri, A.Hu, L.Delouvroy, F.Vermeiren, K.Vandercruyssen, G.Van der Helm, L.Cleiren, E.Mostmans, W.Lory, P.Pille, G.Van Emelen, K.Fanning, G.Pauwels, F.Lin, T.I.Simmen, K.Raboisson, P.

(2009) Bioorg Med Chem Lett 19: 2492-2496

  • DOI: https://doi.org/10.1016/j.bmcl.2009.03.035
  • Primary Citation of Related Structures:  
    3GOL

  • PubMed Abstract: 

    Optimization through parallel synthesis of a novel series of hepatitis C virus (HCV) NS5B polymerase inhibitors led to the identification of (R)-11-(4-benzyloxy-2-fluorophenyl)-6-hydroxy-3,3-dimethyl-10-(6-methylpyridine-2-carbonyl)-2,3,4,5,10,11-hexahydro-dibenzo[b,e][1,4]diazepin-1-one 11zc and (R)-11-(4-benzyloxy-2-fluorophenyl)-6-hydroxy-3,3-dimethyl-10-(2,5-dimethyloxazol-4-carbonyl)-2,3,4,5,10,11-hexahydro-dibenzo[b,e][1,4]diazepin-1-one 11zk as potent (replicon EC(50)=400nM and 270nM, respectively) and selective (CC(50)>20muM) inhibitors of HCV replication. These data warrant further lead-optimization efforts.


  • Organizational Affiliation

    Tibotec BVBA, Gen. De Wittelaan L11 B3, B-2800 Mechelen, Belgium.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA-directed RNA polymerase
A, B
581Hepatitis 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
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
XND PDBBind:  3GOL IC50: 81 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.85 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.191 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 106.048α = 90
b = 106.62β = 90
c = 134.679γ = 90
Software Package:
Software NamePurpose
XDSdata scaling
REFMACrefinement
XDSdata reduction
XSCALEdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-06-16
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Source and taxonomy, Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 1.3: 2024-03-20
    Changes: Data collection, Database references, Derived calculations