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


Ligand Structure Quality Assessment 


This is version 1.4 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

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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: 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
  • Version 1.4: 2024-04-03
    Changes: Refinement description