| Thermodynamics of radicicol binding to human Hsp90 alpha and beta isoforms. | |
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MedLine Citation:
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PMID: 20943306 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Radicicol is a natural antibiotic that specifically inhibits chaperone Hsp90 activity and binds to its active site with nanomolar affinity. Radicicol has been widely used as a lead compound to generate synthetic analogs with reduced toxicity and increased stability that could be employed clinically. Here we present a detailed thermodynamic description of radicicol binding to human Hsp90 and yeast Hsc82 studied by isothermal titration calorimetry and thermal shift assay. Titrations as a function of pH showed a linked protonation event upon radicicol binding. The intrinsic binding constant and the thermodynamic parameters (including the enthalpy, entropy, and heat capacity) were determined for yeast Hsc82, and human alpha and beta Hsp90. Recent experimental evidence in literature shows that yeast Hsc82 has significant differences from human Hsp90 isozymes. Here we support this by demonstrating differences in radicicol binding thermodynamics to these proteins. The intrinsic enthalpy of radicicol binding to Hsc82 was -46.7 kJ/mol, to Hsp90alpha -70.7 kJ/mol, and to Hsp90beta was -66.8 kJ/mol. The enthalpies of binding were significantly different, while the intrinsic dissociation constants were quite similar, equal to 0.25, 0.04, and 0.15 nM, respectively. The structural features responsible for such large difference in binding enthalpy but small difference in the intrinsic binding Gibbs free energy are discussed. |
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Authors:
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Asta Zubrienė; Malgorzata Gutkowska; Jurgita Matulienė; Romanas Chaleckis; Vilma Michailovienė; Aliona Voroncova; Ceslovas Venclovas; Alicja Zylicz; Maciej Zylicz; Daumantas Matulis |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-12 |
Journal Detail:
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Title: Biophysical chemistry Volume: 152 ISSN: 1873-4200 ISO Abbreviation: Biophys. Chem. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-08 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0403171 Medline TA: Biophys Chem Country: Netherlands |
Other Details:
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Languages: eng Pagination: 153-63 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Laboratory of Biothermodynamics and Drug Design, Institute of Biotechnology, LT-02241 Vilnius, Lithuania. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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