4XDM

N-terminal domain of Hsp90 from Dictyostelium discoideum in complex with Geldanamycin

4XDM の概要

• エントリーDOI: 10.2210/pdb4xdm/pdb
• 関連するPDBエントリー: 4XC0 4XCJ 4XCL 4XD8
• 分子名称: Heat shock cognate 90 kDa protein, GELDANAMYCIN, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• 機能のキーワード: hsp90, geldanamycin, chaperone
• 由来する生物種: Dictyostelium discoideum (Slime mold)
• 細胞内の位置: Cytoplasm : P54651
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29893.63

構造登録者

Raman, S.,Suguna, K. (登録日: 2014-12-19, 公開日: 2015-12-09, 最終更新日: 2023-11-08)

主引用文献

Raman, S.,Singh, M.,Tatu, U.,Suguna, K.
First Structural View of a Peptide Interacting with the Nucleotide Binding Domain of Heat Shock Protein 90
Sci Rep, 5:17015-17015, 2015

PubMed Abstract: The involvement of Hsp90 in progression of diseases like cancer, neurological disorders and several pathogen related conditions is well established. Hsp90, therefore, has emerged as an attractive drug target for many of these diseases. Several small molecule inhibitors of Hsp90, such as geldanamycin derivatives, that display antitumor activity, have been developed and are under clinical trials. However, none of these tested inhibitors or drugs are peptide-based compounds. Here we report the first crystal structure of a peptide bound at the ATP binding site of the N-terminal domain of Hsp90. The peptide makes several specific interactions with the binding site residues, which are comparable to those made by the nucleotide and geldanamycin. A modified peptide was designed based on these interactions. Inhibition of ATPase activity of Hsp90 was observed in the presence of the modified peptide. This study provides an alternative approach and a lead peptide molecule for the rational design of effective inhibitors of Hsp90 function.

PubMed: 26599366
DOI: 10.1038/srep17015

実験手法

X-RAY DIFFRACTION (1.5 Å)