AN INVESTIGATION OF THE BINDING-SITE OF ALPHA(2U)-GLOBULIN USING ISOTOPICALLY LABELED LIGANDS AND INVERSE NUCLEAR-MAGNETIC-RESONANCE TECHNIQUES

A series of isotopically labeled ligands were bound to the protein alp ha(2u)-globulin. These protein complexes were studied using C-13, F-19 , and selective inverse detection NMR experiments to determine chemica l shifts and nuclear Overhauser effect correlations for the labeled si tes of the ligands. The NMR data indicate that the labeled portions of the ligands are located in a highly aromatic region of the alpha(2u)- globulin binding pocket. Molecular modeling based on the NMR data and a medium resolution X-ray crystal structure of alpha(2u)-globulin pred icts a model for ligand binding which is consistant with experimental observations and calculated ring current effects. Conformational chang es in the aromatic region of the binding site upon binding these ligan ds in solution may be supported by this model.