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    Elucidation of the Hsp90 C-terminal Inhibitor Binding Site

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    Matts_ACSChemBiol_2011.pdf (1.744Mb)
    Issue Date
    2011-08-19
    Author
    Matts, Robert L.
    Dixit, Anshuman
    Peterson, Laura B.
    Sun, Liang
    Voruganti, Sudhakar
    Kalyanaraman, Palgunan
    Hartson, Steve D.
    Verkhivker, Gennady M.
    Blagg, Brian S. J.
    Publisher
    ACS Chem Biol.
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Rights
    Copyright © 2011 American Chemical Society
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    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.
    URI
    http://hdl.handle.net/1808/23521
    DOI
    https://doi.org/10.1021/cb200052x
    Collections
    • Medicinal Chemistry Scholarly Works [255]
    Citation
    Matts, R. L., Dixit, A., Peterson, L. B., Sun, L., Voruganti, S., Kalyanaraman, P., … Blagg, B. S. J. (2011). Elucidation of the Hsp90 C-terminal Inhibitor Binding Site. ACS Chemical Biology, 6(8), 800–807. http://doi.org/10.1021/cb200052x

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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