Elucidation of the Hsp90 C-Terminal Inhibitor Binding Site

Citations Over TimeTop 10% of 2011 papers

Abstract

The Hsp90 chaperone machine is required for the folding, activation, and/or stabilization of more than 50 proteins directly related to malignant progression. Hsp90 contains small molecule binding sites at both its N- and C-terminal domains; however, limited structural and biochemical data regarding the C-terminal binding site is available. In this report, the small molecule binding site in the Hsp90 C-terminal domain was revealed by protease fingerprinting and photoaffinity labeling utilizing LC-MS/MS. The identified site was characterized by generation of a homology model for hHsp90α using the SAXS open structure of HtpG and docking the bioactive conformation of NB into the generated model. The resulting model for the bioactive conformation of NB bound to Hsp90α is presented herein.

Related Papers

• → Integration of the accelerator Aha1 in the Hsp90 co-chaperone cycle(2013)127 cited
• → A novel chaperone-activity-reducing mechanism of the 90-kDa molecular chaperone HSP90(1999)77 cited
• → Inhibition of GR‐mediated transcription by p23 requires interaction with Hsp90(2004)46 cited
• → Evidence for chaperone heterocomplexes containing both Hsp90 and VCP(2005)16 cited
• → Structure and function of molecular chaperones: Functions of HSP90, a major stress protein(1998)