3GNV

HCV NS5B polymerase in complex with 1,5 benzodiazepine inhibitor 1b


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.177 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 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
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
XNZ
Query on XNZ

Download Ideal Coordinates CCD File 
C [auth A],
E [auth B]
(11R)-10-acetyl-11-[4-(benzyloxy)-2-chlorophenyl]-6-hydroxy-3,3-dimethyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one
C30 H29 Cl N2 O4
VZBRCRRODKYBEF-LJAQVGFWSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
D [auth A],
F [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
XNZ PDBBind:  3GNV IC50: 93 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.177 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 106.291α = 90
b = 107.965β = 90
c = 133.799γ = 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: 2009-10-20
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Source and taxonomy, Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description