Structure and biological function of human 3-alpha hydroxysteroid dehydrogenase type 3 in breast cancer

摘要: La 3-alpha hydroxysteroide deshydrogenase de type 3 humaine (3α-HSD3) a un role essentiel dans l’inactivation la 5α-dihydrotestosterone (5α-DHT). Par une combinaison mutagenese, cinetique et la cristallographie par rayon-X, nous demontrons que mutation la Valine54 Leucine54 dans 3α-HSD3 reduit sa capacite d’inactivation 5α-DHT ameliore une activite 20-alpha hydroxysteroide deshydrogenase. ailleurs, structure cristalline en complexe avec la 5α-androstane-3,17-dione/epi-androsterone (A-dione/epi-ADT) ete obtenue co-cristallisation, 5α-DHT, ce qui implique que des modes liaison alternative 3α-HSD3. La suppression l’expression ARNsi ne fait pas seulement qu’augmenter concentration les cellules MCF7, mais elle diminue aussi proliferation cellulaire des cellules MCF7 presence 5α-DHT. Le recepteur des estrogenes alpha (ERα) controle le developpement sexuel et les fonctions reproduction. Nous avons mis place methode de purification du fragment l’ERα incluant son domaine a l’ADN au ligand (DBD-LBD). La cristallogenese preliminaire DBD-LBD les elements reponse l’estrogene ete effectuee. ailleurs, nous rapporte purification simple efficace pour l’ERα.%%%%Human hydroxysteroid dehydrogenase has an essential in the inactivation of androgen By a combination mutagenesis, kinetics and X-ray crystallography, we demonstrate that the Valine54 to 3α-HSD3 reduces its inactivation ability enhances 20-alpha hydroxysteroid dehydrogenase activity. Furthermore, crystal structure complex with 5α-androstane-3,17-dione/epi-androsterone is obtained by co-crystallization with which implies that 5α-DHT binding mode within 3α-HSD3. Suppression of expression specific siRNA not only increases 5α-DHT concentration cells, but also decreases cell proliferation Estrogen receptor alpha (ERα) controls sexual development reproductive functions. We establish protocol ERα including DNA binding domain Preliminary crystallogenesis estrogen response elements is carried out. Additionally, we report and efficient method for LBD.