Ligand Binding Promiscuity of Human Liver Fatty Acid Binding Protein: Structural and Dynamic Insights from an Interaction Study with Glycocholate and Oleate. Issue 14 (11th June 2013)

• Record Type: Journal Article
• Authors: Favretto, Filippo; Assfalg, Michael; Gallo, Mariana; Cicero, Daniel Oscar; D'Onofrio, Mariapina; Molinari, Henriette
• Is Part Of: Chembiochem. Volume 14:Issue 14(2013)
• Page Start: 1807
• Page End: 1819
• Publication Date: 2013-06-11
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201300156
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Human liver fatty acid binding protein (hL‐FABP) has been reported to act as an intracellular shuttle of lipid molecules, thus playing a central role in systemic metabolic homeostasis. The involvement of hL‐FABP in the transport of bile salts has been postulated but scarcely investigated. Here we describe a thorough NMR investigation of glycocholate (GCA) binding to hL‐FABP. The protein molecule bound a single molecule of GCA, in contrast to the 1:2 stoichiometry observed with fatty acids. GCA was found to occupy the large internal cavity of hL‐FABP, without requiring major conformational rearrangement of the protein backbone; rather, this led to increased stability, similar to that estimated for the hL‐FABP:oleate complex. Fast‐timescale dynamics appeared not to be significantly perturbed in the presence of ligands. Slow motions (unlike for other proteins of the family) were retained or enhanced upon binding, consistent with a requirement for structural plasticity for promiscuous recognition.</p> </abstract>