The binding of methylsulfonyl-polychloro-biphenyls to uteroglobin

The binding of methylsulfonyl-polychloro-biphenyls (methylsulfonyl-PCBs) to purified uteroglobin was studied by a dextran-coated charcoal assay using 4,4'-bis( 3H]methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl (3H-MeSO2)2TCB] as radiolabeled ligand. The specific binding of this ligand to uteroglobin was enhanced by the presence of dithiothreitol, and the optimal concentration of dithiothreitol for binding was 20 mM. The specific (3H-MeSO2)2TCB] binding was inhibited by 4-methylsulfonyl-2,2',4',5,5'-pentachlorobiphenyl in a concentration-dependent manner. The molecular structures of methylsulfonyl-PCBs, and progesterone, were fitted into the X-ray crystallographic structure of uteroglobin using the molecular graphics program TOM. In these simulations the water-accessible surfaces of the ligands appeared quite similar, and fitted nicely in the internal water-accessible surface of uteroglobulin. Moreover, it appeared from the computer-supported ligand-binding studies that the sulfone oxygens of the studied methylsulfonyl-PCBs, as well as the carbonyl (C20) of progesterone, may form hydrogen bonds with the hydroxyl group of TYR 21 of uteroglobulin. These findings may explain why both steroids and methylsulfonyl-PCBs interact with the same protein, although these two types of ligands are structurally dissimilar.