3INW

HSP90 N-TERMINAL DOMAIN with pochoxime A

Summary for 3INW

• Entry DOI: 10.2210/pdb3inw/pdb
• Related: 3INX
• Descriptor: 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)
• Functional Keywords: alpha beta, 2-layer sandwich, atp-binding, chaperone, nucleotide-binding, phosphoprotein, stress response, sp, ral, radicicol, pochonin, pochoxime
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P07900
• Total number of polymer chains: 1
• Total formula weight: 26227.96

Authors

Korndoerfer, I.P. (deposition date: 2009-08-13, release date: 2010-08-18, Last modification date: 2023-09-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.95 Å)