3INW

HSP90 N-TERMINAL DOMAIN with pochoxime A

3INW の概要

• エントリーDOI: 10.2210/pdb3inw/pdb
• 関連するPDBエントリー: 3INX
• 分子名称: Heat shock protein HSP 90-alpha, DIMETHYL SULFOXIDE, (5E,9E,11E)-13-chloro-14,16-dihydroxy-3,4,7,8-tetrahydro-1H-2-benzoxacyclotetradecine-1,11(12H)-dione 11-[O-(2-oxo-2-piperidin-1-ylethyl)oxime], ... (4 entities in total)
• 機能のキーワード: alpha beta, 2-layer sandwich, atp-binding, chaperone, nucleotide-binding, phosphoprotein, stress response, sp, ral, radicicol, pochonin, pochoxime
• 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: 26227.96

構造登録者

Korndoerfer, I.P. (登録日: 2009-08-13, 公開日: 2010-08-18, 最終更新日: 2023-09-06)

主引用文献

Barluenga, S.,Fontaine, J.G.,Wang, C.,Aouadi, K.,Chen, R.,Beebe, K.,Neckers, L.,Winssinger, N.
Inhibition of HSP90 with pochoximes: SAR and structure-based insights.
Chembiochem, 10:2753-2759, 2009

PubMed Abstract: The pochoximes, based on the radicicol pharmacophore, are potent inhibitors of heat shock protein 90 (HSP90) that retain their activity in vivo. Herein we report an extended library that broadly explores the structure-activity relationship (SAR) of the pochoximes with four points of diversity. Several modifications were identified that afford improved cellular efficacy, new opportunities for conjugation, and further diversifications. Cocrystal structures of pochoximes A and B with HSP90 show that pochoximes bind to a different conformation of HSP90 than radicicol and provide a rationale for the enhanced affinity of the pochoximes relative to radicicol and the pochonins.

PubMed: 19856365
DOI: 10.1002/cbic.200900494

実験手法

X-RAY DIFFRACTION (1.95 Å)