2DXS

Crystal structure of HCV NS5B RNA polymerase complexed with a tetracyclic inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.219 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Discovery of Conformationally Constrained Tetracyclic Compounds as Potent Hepatitis C Virus NS5B RNA Polymerase Inhibitors

Ikegashira, K.Oka, T.Hirashima, S.Noji, S.Yamanaka, H.Hara, Y.Adachi, T.Tsuruha, J.Doi, S.Hase, Y.Noguchi, T.Ando, I.Ogura, N.Ikeda, S.Hashimoto, H.

(2006) J Med Chem 49: 6950-6953

  • DOI: https://doi.org/10.1021/jm0610245
  • Primary Citation of Related Structures:  
    2DXS

  • PubMed Abstract: 

    We report a new series of hepatitis C virus NS5B RNA polymerase inhibitors containing a conformationally constrained tetracyclic scaffold. SAR studies led to the identification of 6,7-dihydro-5H-benzo[5,6][1,4]diazepino[7,1-a]indoles (19 and 20) bearing a basic pendent group with high biochemical and cellular potencies. These compounds displayed a very small shift in cellular potency when the replicon assay was performed in the presence of human serum albumin.


  • Organizational Affiliation

    Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan. kazutaka.ikegashira@ims.jti.co.jp


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Genome polyprotein
A, B
552Hepacivirus hominisMutation(s): 0 
Gene Names: 1B
EC: 2.7.7.48
UniProt
Find proteins for P26663 (Hepatitis C virus genotype 1b (isolate BK))
Explore P26663 
Go to UniProtKB:  P26663
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP26663
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
JTP
Query on JTP

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
N-[(13-CYCLOHEXYL-6,7-DIHYDROINDOLO[1,2-D][1,4]BENZOXAZEPIN-10-YL)CARBONYL]-2-METHYL-L-ALANINE
C27 H30 N2 O4
LNQWELVSNCYKDU-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
JTP PDBBind:  2DXS IC50: 46 (nM) from 1 assay(s)
Binding MOAD:  2DXS IC50: 46 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.219 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 96.454α = 90
b = 67.231β = 93.78
c = 97.853γ = 90
Software Package:
Software NamePurpose
CNXrefinement
MOSFLMdata reduction
CCP4data scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-12-26
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description