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.
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