3GNW

HCV NS5B polymerase in complex with 1,5 benzodiazepine inhibitor 4c

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.39 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.167 
  • R-Value Observed: 0.169 

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Ligand Structure Quality Assessment 


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


Literature

Structure-based design of a benzodiazepine scaffold yields a potent allosteric inhibitor of hepatitis C NS5B RNA polymerase.

Vandyck, K., Cummings, M.D., Nyanguile, O., Boutton, C.W., Vendeville, S., McGowan, D., Devogelaere, B., Amssoms, K., Last, S., Rombauts, K., Tahri, A., Lory, P., Hu, L., Beauchamp, D.A., Simmen, K., Raboisson, P.

(2009) J Med Chem 52: 4099-4102

  • DOI: https://doi.org/10.1021/jm9005548
  • Primary Citation of Related Structures:  
    3GNV, 3GNW

  • PubMed Abstract: 

    HCV NS5B polymerase, an essential and virus-specific enzyme, is an important target for drug discovery. Using structure-based design, we optimized a 1,5-benzodiazepine NS5B polymerase inhibitor chemotype into a new sulfone-containing scaffold. The design yielded potent inhibitor (S)-4c (K(D) = 0.79 nM), which has approximately 20-fold greater affinity for NS5B than its carbonyl analogue (R)-2c.

    • Organizational Affiliation: 

    Tibotec BVBA, Generaal de Wittelaan L 11B 3, 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
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
XNC PDBBind:  3GNW Kd: 0.79 (nM) from 1 assay(s)
Binding MOAD:  3GNW Kd: 0.79 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.39 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.167 
  • R-Value Observed: 0.169 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 106.534α = 90
b = 107.573β = 90
c = 133.657γ = 90
Software Package:
Software NamePurpose
XDSdata scaling
REFMACrefinement
XDSdata reduction
XSCALEdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-10-20
    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: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description