3ANS

Human soluble epoxide hydrolase in complex with a synthetic inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.98 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.221 

Starting Model: experimental
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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted S38Click on this verticalbar to view details

This is version 1.4 of the entry. See complete history


Literature

A practical use of ligand efficiency indices out of the fragment-based approach: ligand efficiency-guided lead identification of soluble epoxide hydrolase inhibitors

Tanaka, D.Tsuda, Y.Shiyama, T.Nishimura, T.Chiyo, N.Tominaga, Y.Sawada, N.Mimoto, T.Kusunose, N.

(2011) J Med Chem 54: 851-857

  • DOI: https://doi.org/10.1021/jm101273e
  • Primary Citation of Related Structures:  
    3ANS, 3ANT

  • PubMed Abstract: 

    Ligand efficiency is frequently used to evaluate fragment compounds in fragment-based drug discovery. We applied ligand efficiency indices in a conventional virtual screening-initiated lead generation study of soluble epoxide hydrolase inhibitors. From a considerable number of screening hits, we carefully selected a compound exhibiting relatively weak inhibitory activity but high ligand efficiency. This ligand efficiency-guided selection could reveal compounds possessing preferable lead-like characteristics in terms of molecular size and lipophilicity. The following hit-to-lead medicinal chemistry campaign successfully led to a more potent, ADMET-clean, lead-like compound preserving high ligand efficiency. Retrospective analyses, including consideration of the more recently proposed indices of ligand efficiency, shed light on the validity of our hit triage and hit-to-lead studies. The present work proposes a practical methodology for lead generation using the concept of ligand efficiency.


  • Organizational Affiliation

    Chemistry Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd. 3-1-98 Kasugade-naka, Konohana, Osaka 554-0022, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Epoxide hydrolase 2
A, B
336Homo sapiensMutation(s): 0 
Gene Names: EPHX2
EC: 3.3.2.10 (PDB Primary Data), 3.1.3.76 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for P34913 (Homo sapiens)
Explore P34913 
Go to UniProtKB:  P34913
PHAROS:  P34913
GTEx:  ENSG00000120915 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP34913
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
S38 BindingDB:  3ANS IC50: 565 (nM) from 1 assay(s)
PDBBind:  3ANS IC50: 565 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.98 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.221 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 129.63α = 90
b = 80.35β = 126.2
c = 88.69γ = 90
Software Package:
Software NamePurpose
d*TREKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
CrystalCleardata collection
CrystalCleardata reduction
CrystalCleardata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted S38Click on this verticalbar to view details

Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-01-19
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2014-01-22
    Changes: Database references
  • Version 1.3: 2021-02-24
    Changes: Advisory, Database references, Derived calculations
  • Version 1.4: 2023-11-01
    Changes: Data collection, Database references, Refinement description