Unsaturated Δ4,9 and Δ4,9,11 steroid hormones with a keto group in position 3 and a hydroxy, lactone or oxathiolane function in 17β, with or without methyl substituents in positions 17α, 18 and/or 7α, tend to compete significantly for specific binding to the receptor proteins corresponding to several steroid hormone classes (progestin, androgen, mineralo- and glucocorticoid). If the interaction between ligand and receptor protein is compared to a lock-and-key fit, the presence of several common structural features among ligands binding to the receptor proteins of different hormone classes suggests a close affiliation among these proteins; the ability of any one ligand to bind effectively to more than one receptor implies a degree of conformational adaptability exceeding that of the natural hormones. The molecular flexibility and mobility of several Δ4,9 and Δ4,9,11 unsaturated steroids has been established by X-ray crystallography and by molecular geometry calculations and confronted with the corresponding binding specificity profiles. On the basis of these data, it is suggested that the lock-and-key image of complex formation is too static and that the overall steroid- cum -protein flexibility determines complex kinetics and biological response. Furthermore, in view of the limited amount of energy necessary for between-conformer transition ( . < 2 kcal for gestrinone for a flexibility range of Å) compared to the energy of binding to steroid receptors ( K D = 10 −9 M − −12kcal/mol), the in vivo formation of complexes of varying stability with the different conformers of a steroid is quite feasible.
λ- Escherichia coli complexes exhibited remarkable sensitivity to the treatment with test steroidal derivatives in the presence of Cu(II). The decline in plaque-forming units after steroid treatment was more pronounced in complexes with some of the irradiation repair-defective mutants of E. coli K-12, ., recA, lexA and polA , as compared to uvrA and wild-type strains. The red gene of λ phage and recA gene of E. coli seem to have a complementary effect on the steroid-induced lesions. An enhanced level of mutagenesis was observed when steroid-treated E. coli cells were transformed with steroid-treated pBR322 plasmid DNA. A remarkable degree of c mutation was also observed when steroid I-treated phage particles were allowed to adsorb on steroid-treated wild-type bacteria. Moreover, the oxathione steroid treatment of λ cI 857- E. coli lysogen resulted in prophage induction in nutrient broth even at 32°C. Thus on the basis of these results, the role of SOS repair system in steroid-induced mutagenesis and repair of DNA lesions in E. coli and bacteriophage λ has been suggested.