Crystals of the adipocyte lipid-binding protein which diffract to near atomic resolution have been obtained in Na/K phosphate buffer/precipitant system. The structures of the apo-form and the protein with bound oleic acid and stearic acid have been determined and refined to 1.6-Å resolution with R-factor around 18%. The conformations of the bound fatty acids are nearly the same. In both cases, the carboxylate group of the ligand interacts directly with Arg126 and Tyr128, indirectly with Arg106 through a water molecule. The hydrocarbon tail sticks out of the protein surface through a hydrophobic patch. Saturated and unsaturated fatty acids bind in essentially the same conformation. The remaining space of the binding pocket is filled with well ordered water molecules interacting with most of the polar side chains. Comparisons between the holo- and apostructures reveal that the hydrophobic patch on the protein surface formed by a helix and several tight turns might serve as a portal for lipid binding. Since the adipocyte lipid-binding protein is phosphorylated at Tyr19 by the insulin receptor kinase, the position of this side chain has been re-evaluated using the coordinates of the holo-forms. It appears that the position of Tyr19 does not change significantly upon the binding of either of the fatty acids.
|Original language||English (US)|
|Number of pages||11|
|Journal||Journal of Biological Chemistry|
|State||Published - 1993|