A comparative study of estramustine and pregnenolone binding to prostatic binding protein: evidence for subunit cooperativity.
The binding of estramustine, a nitrogen mustard derivative of oestradiol to purified rat prostatic binding protein was studied as a test for a possible identity between this protein and the very similar estramustine-binding protein, described by Forsgren et al. In accordance with this hypothesis estramustine binds to purified prostatic binding protein with a high affinity (2.5 X 10(7)M-1). This affinity markedly exceeds the affinity of pregnenolone for this protein (0.9 X 10(6)M-1) or for a complex of prostatic binding protein, with prostatic proline-rich polypeptide, (4.7 X 10(6)M-1). In competition experiments estramustine completely suppresses the binding of [3H]pregnenolone, whereas the binding of [3H]estramustine is only partially suppressed by pregnenolone, even at high concentrations. Prostatic binding protein was separated in its F- and S-subunit by DEAE-Sepharose chromatography performed in the presence of 8 M urea. Only the S-subunit, most probably in its dimer form, displays marked estramustine and pregnenolone binding, with affinities of respectively 3.7 and 1.2 X 10(6)M-1. Recombination of both subunits results in a strong increase of estramustine binding, but not of pregnenolone binding.
D000727:Androgen-Binding Protein / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism*; D004961:Estramustine / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D009588:Nitrogen Mustard Compounds / Q000378:metabolism*; D011284:Pregnenolone / Q000378:metabolism*; D060789:Prostatein; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D060765:Secretoglobins; D014598:Uteroglobin; D060788:Mammaglobin B
D000727:Androgen-Binding Protein; D002352:Carrier Proteins; D004961:Estramustine; D046911:Macromolecular Substances; D009588:Nitrogen Mustard Compounds; D011284:Pregnenolone; D060789:Prostatein; D060765:Secretoglobins; D014598:Uteroglobin; C511484:Scgb1d2 protein, rat; C511483:Scgb1d4 protein, rat; C556468:Scgb2a1 protein, rat; D060788:Mammaglobin B