STRUCTURE OF 17-(-ESTRADIOL BENZOATE AND ITS INTERACTION WITH TAF-2 DOMAIN OF ESTROGEN RECEPTOR (ER) BY MODELING. Vctor Bolaos-Garca^1,2, Gabriela Jurez-Martnez¹, Enrique Rudio-Piera¹, Kaliyamoorthy Panneerselvam¹ and Manuel Soriano-Garca¹. ¹Instituto de Qumica, UNAM, ²Instituto de Fisiologa Celular, UNAM, Circuito Exterior, Ciudad Universitaria, Deleg. Coyoacn 04510. Mxico, D.F.

This work presents the molecular structure of 17 -estradiol benzoate, which was solved by X-ray diffraction, and proposed a model for 17 -estradiol benzoate-TAF-2 domain interaction. It is an estrogen regulated target cell proliferation, growth, and differentiation through a defined sequence of molecular events triggered by their binding to the intracellular estrogen receptor (ER). The transcriptional activation is mediated by TAF-1 in the N-terminal domain which corresponds to DNA binding domain and TAF-2, which is localized in the C-terminal end and corresponds to the hormone binding domain. Although, essential aspects about TAF-2 structure remains largely unknown. We demonstrated that this domain belongs to a class A amphipathic helix based in Eisenberg hydrophobic moment (_H = 0.42 Kcal/mol per residue) and polar residues distribution. Aditionally, based in surface pressure calculation, the active surface is higher (43.87 mN/m) in comparison with other transcriptional activator protein domains and resemble some features presented in lipid transfer proteins. By molecular modeling it is estimated the importance of polar residues in TAF-2 domain and proposed a mechanism in order to explain the 17 (-estradiol benzoate-TAF-2 interaction at molecular level.

Interestingly, these findings would be valid for other hormone receptors as glucocorticoids and progestins.