4NH7

Correlation between chemotype-dependent binding conformations of HSP90 alpha/beta and isoform selectivity

4NH7 の概要

• エントリーDOI: 10.2210/pdb4nh7/pdb
• 関連するPDBエントリー: 4NH8
• 分子名称: Heat shock protein HSP 90-alpha, 4-[6,6-dimethyl-4-oxidanylidene-3-(trifluoromethyl)-5,7-dihydroindazol-1-yl]-2-[(4-oxidanylcyclohexyl)amino]benzamide, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: a/b fold, chaperone
• 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: 2
• 化学式量合計: 53756.23

構造登録者

Zuccola, H.J.,Ernst, J. (登録日: 2013-11-04, 公開日: 2014-01-15, 最終更新日: 2024-02-28)

主引用文献

Ernst, J.T.,Liu, M.,Zuccola, H.,Neubert, T.,Beaumont, K.,Turnbull, A.,Kallel, A.,Vought, B.,Stamos, D.
Correlation between chemotype-dependent binding conformations of HSP90 alpha / beta and isoform selectivity-Implications for the structure-based design of HSP90 alpha / beta selective inhibitors for treating neurodegenerative diseases.
Bioorg.Med.Chem.Lett., 24:204-208, 2014

PubMed Abstract: HSP90 continues to be a target of interest for neurodegeneration indications. Selective knockdown of the HSP90 cytosolic isoforms α and β is sufficient to reduce mutant huntingtin protein levels in vitro. Chemotype-dependent binding conformations of HSP90α/β appear to strongly influence isoform selectivity. The rational design of HSP90α/β inhibitors selective versus the mitochondrial (TRAP1) and endoplasmic reticulum (GRP94) isoforms offers a potential mitigating strategy for mechanism-based toxicities. Better tolerated HSP90 inhibitors would be attractive for targeting chronic neurodegenerative diseases such as Huntington's disease.

PubMed: 24332488
DOI: 10.1016/j.bmcl.2013.11.036

実験手法

X-RAY DIFFRACTION (2 Å)