1YES

HUMAN HSP90 GELDANAMYCIN-BINDING DOMAIN, "OPEN" CONFORMATION

1YES の概要

• エントリーDOI: 10.2210/pdb1yes/pdb
• 分子名称: HEAT SHOCK PROTEIN 90 (2 entities in total)
• 機能のキーワード: chaperone protein, geldanamycin, signal transduction, heat shock
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P07900
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25670.79

構造登録者

Stebbins, C.E.,Russo, A.A.,Pavletich, N.P. (登録日: 1997-03-25, 公開日: 1998-04-22, 最終更新日: 2024-02-14)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.2 Å)