beta-lactoglobulin binds palmitate within its central cavity

Bovine beta-lactoglobulin (beta-Lg) has been studied extensively in both th e isolated and the naturally occurring states. It is a commercially importa nt whey protein of obvious nutritional value but, so far, one that has no c learly identified biological function. In common with many of the other mem bers of the lipocalin family to which it belongs, beta-Lg binds hydrophobic ligands, and it appears possible that there are at least two distinct bind ing sites per monomer for a variety of ligands, By comparison with other me mbers of the family, there is a probable binding site in the central cavity of the molecule that is formed by the eight antiparallel beta-strands that are typical of the lipocalins, We have now cocrystallized beta-Lg with pal mitic acid, and the refined structure (R = 0.204, R-free = 0.240 for 6,888 reflections to 2.5-Angstrom resolution) reveals that the ligand binds in th e central cavity in a manner similar to the binding of retinol to the relat ed lipocalin, serum retinol-binding protein. The carboxyl group binds to bo th Lys-60 and Lys-69 at the entrance to the cavity. The hydrophobic tail st retches in an almost fully extended conformation into the center of the pro tein. This is the first direct observation of a ligand binding to beta-Lg.