3H98

Crystal structure of HCV NS5b 1b with (1,1-dioxo-2H-[1,2,4]benzothiadiazin-3-yl) azolo[1,5-a]pyrimidine derivative


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.211 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

HCV NS5B polymerase inhibitors 2: Synthesis and in vitro activity of (1,1-dioxo-2H-[1,2,4]benzothiadiazin-3-yl) azolo[1,5-a]pyridine and azolo[1,5-a]pyrimidine derivatives.

Wang, G.Lei, H.Wang, X.Das, D.Hong, J.Mackinnon, C.H.Coulter, T.S.Montalbetti, C.A.Mears, R.Gai, X.Bailey, S.E.Ruhrmund, D.Hooi, L.Misialek, S.Rajagopalan, P.T.Cheng, R.K.Barker, J.J.Felicetti, B.Schonfeld, D.L.Stoycheva, A.Buckman, B.O.Kossen, K.Seiwert, S.D.Beigelman, L.

(2009) Bioorg Med Chem Lett 19: 4480-4483

  • DOI: https://doi.org/10.1016/j.bmcl.2009.05.022
  • Primary Citation of Related Structures:  
    3H98

  • PubMed Abstract: 

    (1,1-Dioxo-2H-[1,2,4]benzothiadiazin-3-yl) azolo[1,5-a]pyridine and azolo[1,5-a]pyrimidine derivatives have been investigated as potential anti-HCV drugs. Their synthesis, HCV NS5B polymerase inhibition, and replicon activity are discussed.


  • Organizational Affiliation

    Discovery Research, InterMune, Inc., Brisbane, CA 94005, USA. gyiwang@yahoo.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA-directed RNA polymerase
A, B
576Hepatitis C virus (isolate BK)Mutation(s): 0 
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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
B5P
Query on B5P

Download Ideal Coordinates CCD File 
C [auth A],
E [auth B]
N-{3-[5-hydroxy-8-(3-methylbutyl)-7-oxo-7,8-dihydroimidazo[1,2-a]pyrimidin-6-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}methanesulfonamide
C19 H22 N6 O6 S2
HJSHQVOBZCLIRI-UHFFFAOYSA-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
B5P PDBBind:  3H98 IC50: 5 (nM) from 1 assay(s)
Binding MOAD:  3H98 IC50: 5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.211 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 85.931α = 90
b = 106.196β = 90
c = 126.417γ = 90
Software Package:
Software NamePurpose
DNAdata collection
PHASERphasing
REFMACrefinement
CrystalCleardata reduction
CrystalCleardata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2009-10-13
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description