Abstract
The activation of molecular chaperone heat-shock protein 90 (Hsp90) is dependent on ATP binding and hydrolysis, which occurs in the N-terminal domains of protein. Here, we have determined three crystal structures of the N-terminal domain of human Hsp90 in native and in complex with ATP and ATP analog, providing a clear view of the catalytic mechanism of ATP hydrolysis by Hsp90. Additionally, the binding of ATP leads the N-terminal domains to be an intermediate state that could be used to partially explain why the isolated N-terminal domain of Hsp90 has very weak ATP hydrolytic activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / analogs & derivatives
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Adenosine Triphosphate / chemistry*
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Adenosine Triphosphate / metabolism
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Amino Acid Sequence
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Binding Sites / genetics
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Crystallography, X-Ray
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HSP90 Heat-Shock Proteins / chemistry*
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HSP90 Heat-Shock Proteins / genetics
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HSP90 Heat-Shock Proteins / metabolism
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Humans
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Hydrolysis
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Models, Molecular
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Molecular Sequence Data
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Protein Binding
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Protein Structure, Secondary
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Protein Structure, Tertiary*
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Sequence Homology, Amino Acid
Substances
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HSP90 Heat-Shock Proteins
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5'-adenylyl (beta,gamma-methylene)diphosphonate
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Adenosine Triphosphate