3BR9

Crystal Structure of HCV NS5B Polymerase with a Novel Pyridazinone Inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.195 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Novel HCV NS5B polymerase inhibitors derived from 4-(1',1'-dioxo-1',4'-dihydro-1'lambda6-benzo[1',2',4']thiadiazin-3'-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 1: exploration of 7'-substitution of benzothiadiazine.

Zhou, Y.Webber, S.E.Murphy, D.E.Li, L.S.Dragovich, P.S.Tran, C.V.Sun, Z.Ruebsam, F.Shah, A.M.Tsan, M.Showalter, R.E.Patel, R.Li, B.Zhao, Q.Han, Q.Hermann, T.Kissinger, C.R.Lebrun, L.Sergeeva, M.V.Kirkovsky, L.

(2008) Bioorg Med Chem Lett 18: 1413-1418

  • DOI: https://doi.org/10.1016/j.bmcl.2008.01.007
  • Primary Citation of Related Structures:  
    3BR9, 3BSA, 3BSC

  • PubMed Abstract: 

    5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as inhibitors of genotype 1 HCV NS5B polymerase. The synthesis, structure-activity relationships (SAR), metabolic stability, and structure-based design approach for this new class of compounds are discussed.


  • Organizational Affiliation

    Anadys Pharmaceuticals, Inc., 3115 Merryfield Row, San Diego, CA 92121, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA-directed RNA polymerase
A, B
578Hepacivirus hominisMutation(s): 1 
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
DEY
Query on DEY

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
(2R)-2-({3-[5-hydroxy-2-(3-methylbutyl)-3-oxo-6-thiophen-2-yl-2,3-dihydropyridazin-4-yl]-1,1-dioxido-2H-1,2,4-benzothia diazin-7-yl}oxy)propanamide
C23 H25 N5 O6 S2
BPHLZVCJUQBQLM-CYBMUJFWSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
DEY PDBBind:  3BR9 IC50: 62 (nM) from 1 assay(s)
Binding MOAD:  3BR9 IC50: 62 (nM) from 1 assay(s)
BindingDB:  3BR9 IC50: 62 (nM) from 1 assay(s)
EC50: 210 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.195 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 84.502α = 90
b = 104.311β = 90
c = 125.693γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
CrystalCleardata collection
DENZOdata reduction
SCALEPACKdata scaling
EPMRphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-12-23
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-20
    Changes: Database references, Derived calculations, Structure summary
  • Version 1.3: 2024-02-21
    Changes: Data collection