2ZIR

Crystal Structure of rat protein farnesyltransferase complexed with a benzofuran inhibitor and FPP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.195 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Synthesis and structure-activity relationships of novel benzofuran farnesyltransferase inhibitors

Asoh, K.Kohchi, M.Hyoudoh, I.Ohtsuka, T.Masubuchi, M.Kawasaki, K.Ebiike, H.Shiratori, Y.Fukami, T.A.Kondoh, O.Tsukaguchi, T.Ishii, N.Aoki, Y.Shimma, N.Sakaitani, M.

(2009) Bioorg Med Chem Lett 19: 1753-1757

  • DOI: https://doi.org/10.1016/j.bmcl.2009.01.074
  • Primary Citation of Related Structures:  
    2ZIR, 2ZIS

  • PubMed Abstract: 

    A series of benzofuran-based farnesyltransferase inhibitors have been designed and synthesized as antitumor agents. Among them, 11f showed the most potent enzyme inhibitory activity (IC(50)=1.1nM) and antitumor activity in human cancer xenografts in mice.


  • Organizational Affiliation

    Kamakura Research Laboratories, Chugai Pharmaceutical Co. Ltd., 200-Kajiwara, Kamakura, Kanagawa 247-8530, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protein farnesyltransferase subunit alpha377Rattus norvegicusMutation(s): 1 
Gene Names: Fnta
EC: 2.5.1.58
UniProt
Find proteins for Q04631 (Rattus norvegicus)
Explore Q04631 
Go to UniProtKB:  Q04631
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ04631
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Protein farnesyltransferase subunit beta440Rattus norvegicusMutation(s): 0 
Gene Names: Fntb
EC: 2.5.1.58
UniProt
Find proteins for Q02293 (Rattus norvegicus)
Explore Q02293 
Go to UniProtKB:  Q02293
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ02293
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NH7
Query on NH7

Download Ideal Coordinates CCD File 
G [auth B]2-[(S)-(4-chlorophenyl)(hydroxy)(1-methyl-1H-imidazol-5-yl)methyl]-N-morpholin-4-yl-7-phenyl-1-benzofuran-5-carboxamide
C30 H27 Cl N4 O4
DEXSDZQNSUQUAY-PMERELPUSA-N
FPP
Query on FPP

Download Ideal Coordinates CCD File 
F [auth B]FARNESYL DIPHOSPHATE
C15 H28 O7 P2
VWFJDQUYCIWHTN-YFVJMOTDSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
H [auth B],
I [auth B],
J [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
E [auth B]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
FPP BindingDB:  2ZIR Kd: 2 (nM) from 1 assay(s)
NH7 BindingDB:  2ZIR IC50: 6.4 (nM) from 1 assay(s)
Binding MOAD:  2ZIR IC50: 6.4 (nM) from 1 assay(s)
PDBBind:  2ZIR IC50: 6.4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.195 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 171.996α = 90
b = 171.996β = 90
c = 69.179γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
CNXrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-02-24
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description