Effect of Heldanamycin Binding on the Thr90 Phosphorylation Site of Hsp90

Prostate cancer is hormone-dependent and the androgen receptor (AR) involved in its development. AR a transcription factor that activated by ligand binding, result translocation into nucleus, where it initiates gene transcription. In an inactive state cytoplasm exists as complex with heat shock protein 90 (HSP90) some other proteins. When agonist binds, conformational change occurs, resulting HSP90 chaperones dissociating. Recently has been shown for dissociation of HSP90-AR latter phosphorylation Thr-90 residue N-terminal domain necessary. this work, effect inhibitor, heldanamycin, interacting ATP-binding site, on Thr90 site was investigated molecular modeling methods. It inhibitor binding slightly affects size mobility cavity around Thr90. suggested to does not changing structure influence phosphorylation, partially explains low effectiveness such type drugs therapy prostate cancer.