3P6H

Human adipocyte lipid-binding protein FABP4 in complex with (S)-ibuprofen


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.15 Å
  • R-Value Free: 0.191 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.160 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structural analysis of ibuprofen binding to human adipocyte fatty-acid binding protein (FABP4).

Gonzalez, J.M.Fisher, S.Z.

(2015) Acta Crystallogr F Struct Biol Commun 71: 163-170

  • DOI: https://doi.org/10.1107/S2053230X14027897
  • Primary Citation of Related Structures:  
    3P6C, 3P6D, 3P6E, 3P6F, 3P6G, 3P6H, 3RZY

  • PubMed Abstract: 

    Inhibition of human adipocyte fatty-acid binding protein (FABP4) has been proposed as a treatment for type 2 diabetes, fatty liver disease and atherosclerosis. However, FABP4 displays a naturally low selectivity towards hydrophobic ligands, leading to the possibility of side effects arising from cross-inhibition of other FABP isoforms. In a search for structural determinants of ligand-binding selectivity, the binding of FABP4 towards a group of small molecules structurally related to the nonsteroidal anti-inflammatory drug ibuprofen was analyzed through X-ray crystallography. Several specific hydrophobic interactions are shown to enhance the binding affinities of these compounds, whereas an aromatic edge-to-face interaction is proposed to determine the conformation of bound ligands, highlighting the importance of aromatic interactions in hydrophobic environments.


  • Organizational Affiliation

    Protein Crystallography Station, Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Fatty acid-binding protein, adipocyte139Homo sapiensMutation(s): 0 
Gene Names: FABP4
UniProt & NIH Common Fund Data Resources
Find proteins for P15090 (Homo sapiens)
Explore P15090 
Go to UniProtKB:  P15090
PHAROS:  P15090
GTEx:  ENSG00000170323 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP15090
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
IBP
Query on IBP

Download Ideal Coordinates CCD File 
B [auth A]IBUPROFEN
C13 H18 O2
HEFNNWSXXWATRW-JTQLQIEISA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.15 Å
  • R-Value Free: 0.191 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.160 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 32.328α = 90
b = 53.38β = 90
c = 75.031γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALAdata scaling
AMoREphasing
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-04-13
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2015-02-11
    Changes: Database references
  • Version 1.3: 2015-02-25
    Changes: Database references
  • Version 1.4: 2024-02-21
    Changes: Data collection, Database references, Derived calculations