X-RAY CRYSTALLOGRAPHIC STRUCTURES OF ADIPOCYTE LIPID-BINDING PROTEIN COMPLEXED WITH PALMITATE AND HEXADECANESULFONIC ACID - PROPERTIES OF CAVITY BINDING-SITES

Adipocyte lipid-binding protein is a 14.6-kDa polypeptide that is resp onsible for the intracellular trafficking of fatty acids. Its structur e previously has been solved in the apo and hole forms complexed with stearate and oleate. To examine the binding of lipids other than those with a carboxylate headgroup, we have determined the structure of ALB P in complex with a sulfonic acid, hexadecanesulfonic acid, and compar ed its structure with the natural fatty acid analog, palmitate. Crysta llographic refinement led to similar models, both with R-factors of ab out 20% and a resolution of 1.6 Angstrom. These results can be compare d with earlier studies on C-18 fatty acids, both saturated and unsatur ated. The previously refined complexes with stearate and oleate in com bination with the complexes of palmitate and hexadecanesulfonic acid d emonstrate specific positions for water molecules bound in the interna l cavity. Many of the water-binding sites are present in both the apo form and the hole forms of the protein. With ligand present, a network of 10 internalized water molecules appear to form a hydrophobic hydra tion region. In spite of the sp3 geometry of the sulfonic acid derivat ive, the headgroup occupies the same site as that of the planar carbox ylate in natural fatty acids. These results demonstrate that intracell ular lipid-binding proteins are capable of binding a wider variety of lipids than previously considered and reveal the importance of interio r ordered water molecules in the binding cavity.