Backbone dynamics of human liver fatty acid binding protein in complex with oleate and glycocholate

FAVRETTO F.; D'ONOFRIO M.D.; ASSFALG M. ; GALLO M.; CICERO D. ; MOLINARI H.

Mendoza

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Bioquímica y Biología Molecular; 2012

SAIB

Human liver fatty acid binding protein (HLFABP) belongs to the fatty acid binding protein family, a class of small cytosolic proteins able to translocate various lipidic molecules across the cell. It has been proposed that FABPs participate in nuclear signaling and in the regulation of normal lipid homeostasis and have recently been indicated as drug targets against the development of lipid-related disorders. The crystal structure of rat LFABPreveals a significantly larger binding cavity volume (440 Å) compared to those of other intracellular lipid binding proteins (210-330 Å), that allows it to bind two molecules of fatty acids. The aim of this project is to determine the interaction between HLFABP and other molecules of biological relevance. To better understand the binding capacity of this protein Nuclear Magnetic Resonance (NMR) spectroscopy has been employed to study the backbone dynamics of the protein in its apo form, in complex with oleate (OA) and glycocholic acid (GCA). Our results suggest that high frequency motions (10exp8-10exp12 s-1) are only little affected by the addition of the two ligands. On the other side, the addition of GCA strongly affects frequency motions on a slower time scale (10exp3-10exp6 s-1 ), while the addition of OAdoes not affect significantly these motions.