4E5D

2.2A resolution structure of a firefly luciferase-benzothiazole inhibitor complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.190 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Firefly luciferase in chemical biology: a compendium of inhibitors, mechanistic evaluation of chemotypes, and suggested use as a reporter.

Thorne, N.Shen, M.Lea, W.A.Simeonov, A.Lovell, S.Auld, D.S.Inglese, J.

(2012) Chem Biol 19: 1060-1072

  • DOI: https://doi.org/10.1016/j.chembiol.2012.07.015
  • Primary Citation of Related Structures:  
    4E5D

  • PubMed Abstract: 

    Firefly luciferase (FLuc) is frequently used as a reporter in high-throughput screening assays, owing to the exceptional sensitivity, dynamic range, and rapid measurement that bioluminescence affords. However, interaction of small molecules with FLuc has, to some extent, confounded its use in chemical biology and drug discovery. To identify and characterize chemotypes interacting with FLuc, we determined potency values for 360,864 compounds found in the NIH Molecular Libraries Small Molecule Repository, available in PubChem. FLuc inhibitory activity was observed for 12% of this library with discernible SAR. Characterization of 151 inhibitors demonstrated a variety of inhibition modes, including FLuc-catalyzed formation of multisubstrate adduct enzyme inhibitor complexes. As in some cell-based FLuc reporter assays, compounds acting as FLuc inhibitors yield paradoxical luminescence increases, thus data on compounds acquired from FLuc-dependent assays require careful analysis as described here.


  • Organizational Affiliation

    National Center for Advancing Translational Sciences, Bethesda, MD 20892-3370, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Luciferin 4-monooxygenase550Photinus pyralisMutation(s): 0 
EC: 1.13.12.7
UniProt
Find proteins for P08659 (Photinus pyralis)
Explore P08659 
Go to UniProtKB:  P08659
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08659
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0NJ
Query on 0NJ

Download Ideal Coordinates CCD File 
B [auth A]2-(2-fluorophenyl)-6-methoxy-1,3-benzothiazole
C14 H10 F N O S
PPGLEUILAOUYQO-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
0NJ PDBBind:  4E5D IC50: 600 (nM) from 1 assay(s)
BindingDB:  4E5D IC50: 600 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.190 
  • Space Group: P 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 83.939α = 90
b = 83.939β = 90
c = 96.976γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
JDirectordata collection
HKL-2000data reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-09-05
    Type: Initial release
  • Version 1.1: 2012-09-12
    Changes: Database references
  • Version 1.2: 2017-11-15
    Changes: Refinement description
  • Version 1.3: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description