1YET

GELDANAMYCIN BOUND TO THE HSP90 GELDANAMYCIN-BINDING DOMAIN

Summary for 1YET

• Entry DOI: 10.2210/pdb1yet/pdb
• Descriptor: HEAT SHOCK PROTEIN 90, GELDANAMYCIN (3 entities in total)
• Functional Keywords: chaperone protein, geldanamycin, signal transduction, heat shock
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P07900
• Total number of polymer chains: 1
• Total formula weight: 26231.43

Authors

Stebbins, C.E.,Russo, A.A.,Pavletich, N.P. (deposition date: 1997-03-25, release date: 1998-04-22, Last modification date: 2024-02-14)

Primary citation

Stebbins, C.E.,Russo, A.A.,Schneider, C.,Rosen, N.,Hartl, F.U.,Pavletich, N.P.
Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent.
Cell(Cambridge,Mass.), 89:239-250, 1997

PubMed 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.

PubMed: 9108479
DOI: 10.1016/S0092-8674(00)80203-2

Experimental method

X-RAY DIFFRACTION (1.9 Å)