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Publication Abstract from PubMed

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.

Structural analysis of ibuprofen binding to human adipocyte fatty-acid binding protein (FABP4).,Gonzalez JM, Fisher SZ Acta Crystallogr F Struct Biol Commun. 2015 Feb;71(Pt 2):163-70. doi:, 10.1107/S2053230X14027897. Epub 2015 Jan 28. PMID:25664790^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.