Premium
Structural analysis of ibuprofen binding to human adipocyte fatty‐acid binding protein (FABP4)
Author(s) -
González Javier M.,
Fisher S. Zoë
Publication year - 2015
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x14027897
Subject(s) - fatty acid binding protein , chemistry , nonsteroidal , adipocyte protein 2 , adipocyte , ligand (biochemistry) , binding affinities , selectivity , binding site , biochemistry , fatty acid , gene isoform , small molecule , plasma protein binding , ibuprofen , stereochemistry , receptor , pharmacology , biology , adipose tissue , gene , catalysis
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.