Elucidation of the Hsp90 C-Terminal Inhibitor Binding Site
Year: 2011
Type: article
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.
Source: ACS Chemical Biology
DOI: 10.1021/cb200052x
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G1518323315, G3958390639, Identification of Natural Product Inhibitors of Hsp90 as Chemotherapeutic Agents, Development and Evaluation of Purine and Coumarin Based Hsp90 Inhibitors, Training Grant in Dynamic Aspects of Chemical Biology, G7586217807, Development and Evaluation of Purine and Coumarin Based Hsp90 Inhibitors
OpenAlex ID: W2052697091