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PDBsum entry 1a4h
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References listed in PDB file
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Key reference
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Title
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Identification and structural characterization of the ATP/ADP-Binding site in the hsp90 molecular chaperone.
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Authors
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C.Prodromou,
S.M.Roe,
R.O'Brien,
J.E.Ladbury,
P.W.Piper,
L.H.Pearl.
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Ref.
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Cell, 1997,
90,
65-75.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 3.
Figure 3. Comparison of Bound Nucleotide Conformations in
Hsc70 and Hsp90Conformations of ADP bound to (a) Hsc70 ([13])
and (b) Hsp90. The N1, N6, which make specific contacts in the
ADP/ATP-binding pocket, are indicated, as is the adenine base C8
atom, which is unhindered in the Hsc70-bound conformation but
hindered in the Hsp90-bound conformation.
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Figure 6.
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The above figures are
reprinted
by permission from Cell Press:
Cell
(1997,
90,
65-75)
copyright 1997.
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