Antibiotic radicicol binds to the N-terminal domain of Hsp90 and shares important biologic activities with geldanamycin

Cell Stress Chaperones. 1998 Jun;3(2):100-8. doi: 10.1379/1466-1268(1998)003<0100:arbttn>;2.


The molecular chaperone Hsp90 plays an essential role in the folding and function of important cellular proteins including steroid hormone receptors, protein kinases and proteins controlling the cell cycle and apoptosis. A 15 A deep pocket region in the N-terminal domain of Hsp90 serves as an ATP/ADP-binding site and has also been shown to bind geldanamycin, the only specific inhibitor of Hsp90 function described to date. We now show that radicicol, a macrocyclic antifungal structurally unrelated to geldanamycin, also specifically binds to Hsp90. Moreover, radicicol competes with geldanamycin for binding to the N-terminal domain of the chaperone, expressed either by in vitro translation or as a purified protein, suggesting that radicicol shares the geldanamycin binding site. Radicicol, as does geldanamycin, also inhibits the binding of the accessory protein p23 to Hsp90, and interferes with assembly of the mature progesterone receptor complex. Radicicol does not deplete cells of Hsp90, but rather increases synthesis as well as the steady-state level of this protein, similar to a stress response. Finally, radicicol depletes SKBR3 cells of p185erbB2, Raf-1 and mutant p53, similar to geldanamycin. Radicicol thus represents a structurally unique antibiotic, and the first non-benzoquinone ansamycin, capable of binding to Hsp90 and interfering with its function.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacokinetics*
  • Antifungal Agents / pharmacokinetics*
  • Benzoquinones
  • Binding Sites
  • Binding, Competitive
  • Breast Neoplasms
  • Cell Division / drug effects
  • Chickens
  • Chromatography, Affinity
  • Female
  • HSP90 Heat-Shock Proteins / chemistry*
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Lactams, Macrocyclic
  • Lactones / pharmacokinetics*
  • Lactones / pharmacology*
  • Macrolides
  • Molecular Structure
  • Quinones / pharmacokinetics*
  • Quinones / pharmacology
  • Tumor Cells, Cultured


  • Antibiotics, Antineoplastic
  • Antifungal Agents
  • Benzoquinones
  • HSP90 Heat-Shock Proteins
  • Lactams, Macrocyclic
  • Lactones
  • Macrolides
  • Quinones
  • monorden
  • geldanamycin