Conformational Dynamics of the Molecular Chaperone Hsp90 in Complexes with a Co-chaperone and Anticancer Drugs

Jonathan J. Phillips, Zhongping Yao, Wei Zhang, Stephen McLaughlin, Ernest D. Laue, Carol V. Robinson, Sophie E. Jackson

Research output: Journal article publicationJournal articleAcademic researchpeer-review

39 Citations (Scopus)


The molecular chaperone Hsp90 is essential for the correct folding, maturation and activation of a diverse array of client proteins, including several key constituents of oncogenic processes. Hsp90 has become a focus of cancer research, since it represents a target for direct prophylaxis against multistep malignancy. Hydrogen-exchange mass spectrometry was used to study the structural and conformational changes undergone by full-length human Hsp90β in solution upon binding of the kinase-specific co-chaperone Cdc37 and two Hsp90 ATPase inhibitors: Radicicol and the first-generation anticancer drug DMAG. Changes in hydrogen exchange pattern in the complexes in regions of Hsp90 remote to the ligand-binding site were observed indicating long-range effects. In particular, the interface between the N-terminal domain and middle domains exhibited significant differences between the apo and complexed forms. For the inhibitors, differences in the interface between the middle domain and the C-terminal domain were also observed. These data provide important insight into the structure of the biologically active form of the protein.
Original languageEnglish
Pages (from-to)1189-1203
Number of pages15
JournalJournal of Molecular Biology
Issue number5
Publication statusPublished - 5 Oct 2007
Externally publishedYes


  • anti-cancer drugs
  • co-chaperone
  • Hsp90
  • hydrogen exchange mass spectrometry

ASJC Scopus subject areas

  • Molecular Biology

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