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Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone
journal contribution
posted on 2023-06-08, 14:43 authored by Chrisostomos ProdromouChrisostomos Prodromou, S Mark Roe, Ronan O'Brien, John E Ladbury, Peter W Piper, Laurence PearlLaurence PearlHsp90 molecular chaperones in eukaryotic cells play essential roles in the folding and activation of a range of client proteins involved in cell cycle regulation, steroid hormone responsiveness, and signal transduction. The biochemical mechanism of Hsp90 is poorly understood, and the involvement of ATP in particular is controversial. Crystal structures of complexes between the N-terminal domain of the yeast Hsp90 chaperone and ADP/ATP unambiguously identify a specific adenine nucleotide binding site homologous to the ATP-binding site of DNA gyrase B. This site is the same as that identified for the antitumor agent geldanamycin, suggesting that geldanamycin acts by blocking the binding of nucleotides to Hsp90 and not the binding of incompletely folded client polypeptides as previously suggested. These results finally resolve the question of the direct involvement of ATP in Hsp90 function.
History
Publication status
- Published
Journal
CellISSN
0092-8674Publisher
Elsevier (Cell Press)External DOI
Issue
1Volume
90Page range
65-75Department affiliated with
- Biochemistry Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2015-02-24Usage metrics
Categories
Keywords
Adenosine Diphosphate/*metabolismAmino Acid SequenceAntibioticsAntineoplastic/pharmacologyBenzoquinonesBinding SitesCalorimetryConserved SequenceX-RayDNA GyraseDNA TopoisomerasesType II/chemistry/metabolismHSP90 Heat-Shock Proteins/*chemistry/*metabolismLactamsMacrocyclicModelsMolecularStructuralMolecular Sequence DataProtein Folding*Protein StructureSecondaryQuinones/pharmacologySaccharomyces cerevisiae/metabolismSequence Alignment
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