Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone

Prodromou, Chrisostomos, Roe, S Mark, O'Brien, Ronan, Ladbury, John E, Piper, Peter W and Pearl, Laurence H (1997) Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell, 90 (1). pp. 65-75. ISSN 0092-8674

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Abstract

Hsp90 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.

Item Type: Article
Keywords: Adenosine Diphosphate/*metabolism Amino Acid Sequence Antibiotics, Antineoplastic/pharmacology Benzoquinones Binding Sites Calorimetry Conserved Sequence Crystallography, X-Ray DNA Gyrase DNA Topoisomerases, Type II/chemistry/metabolism HSP90 Heat-Shock Proteins/*chemistry/*metabolism Lactams, Macrocyclic Models, Molecular Models, Structural Molecular Sequence Data Protein Folding *Protein Structure, Secondary Quinones/pharmacology Saccharomyces cerevisiae/metabolism Sequence Alignment
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QD Chemistry > QD0901 Crystallography
Depositing User: Chrisostomos Prodromou
Date Deposited: 24 Feb 2015 17:46
Last Modified: 24 Feb 2015 17:46
URI: http://sro.sussex.ac.uk/id/eprint/44364
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