Effect of Geldanamycin Binding on the Thr90 Phosphorylation Site of Hsp90


  • K.A. Shcherbakov Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia
  • D.S. Shcherbinin Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia
  • A.V. Veselovsky Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia




RIN; amino acid residue interaction network; molecular dynamics; prostate cancer; chaperone HSP90


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


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How to Cite

Shcherbakov, K., Shcherbinin, D., & Veselovsky, A. (2021). Effect of Geldanamycin Binding on the Thr90 Phosphorylation Site of Hsp90. Biomedical Chemistry: Research and Methods, 4(3), e00145. https://doi.org/10.18097/BMCRM00145