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PDBsum entry 4xcl
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References listed in PDB file
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Key reference
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Title
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First structural view of a peptide interacting with the nucleotide binding domain of heat shock protein 90.
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Authors
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S.Raman,
M.Singh,
U.Tatu,
K.Suguna.
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Ref.
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Sci Rep, 2015,
5,
17015.
[DOI no: ]
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PubMed id
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Abstract
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The involvement of Hsp90 in progression of diseases like cancer, neurological
disorders and several pathogen related conditions is well established. Hsp90,
therefore, has emerged as an attractive drug target for many of these diseases.
Several small molecule inhibitors of Hsp90, such as geldanamycin derivatives,
that display antitumor activity, have been developed and are under clinical
trials. However, none of these tested inhibitors or drugs are peptide-based
compounds. Here we report the first crystal structure of a peptide bound at the
ATP binding site of the N-terminal domain of Hsp90. The peptide makes several
specific interactions with the binding site residues, which are comparable to
those made by the nucleotide and geldanamycin. A modified peptide was designed
based on these interactions. Inhibition of ATPase activity of Hsp90 was observed
in the presence of the modified peptide. This study provides an alternative
approach and a lead peptide molecule for the rational design of effective
inhibitors of Hsp90 function.
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