Crystal structure of an Hsp90-geldanamycin complex: Targeting of a protein chaperone by an antitumor agent Academic Article uri icon

Overview

MeSH Major

  • Antibiotics, Antineoplastic
  • HSP90 Heat-Shock Proteins
  • Quinones

abstract

  • The Hsp90 chaperone is required for the activation of several families of eukaryotic protein kinases and nuclear hormone receptors, many of which are protooncogenic and play a prominent role in cancer. The geldanamycin antibiotic has antiproliferative and antitumor effects, as it binds to Hsp90, inhibits the Hsp90-mediated conformational maturation/refolding reaction, and results in the degradation of Hsp90 substrates. The structure of the geldanamycin-binding domain of Hsp90 (residues 9-232) reveals a pronounced pocket, 15 A deep, that is highly conserved across species. Geldanamycin binds inside this pocket, adopting a compact structure similar to that of a polypeptide chain in a turn conformation. This, and the pocket's similarity to substrate-binding sites, suggest that the pocket binds a portion of the polypeptide substrate and participates in the conformational maturation/refolding reaction.

publication date

  • April 18, 1997

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 9108479

Additional Document Info

start page

  • 239

end page

  • 50

volume

  • 89

number

  • 2