4XKO

N-terminal domain of Hsp90 from Dictyostelium discoideum in hexagonal form with PEG

Summary for 4XKO

• Entry DOI: 10.2210/pdb4xko/pdb
• Descriptor: Heat shock cognate 90 kDa protein, DI(HYDROXYETHYL)ETHER, TRIS(HYDROXYETHYL)AMINOMETHANE, ... (4 entities in total)
• Functional Keywords: hsp90, chaperone, peg
• Biological source: Dictyostelium discoideum (Slime mold)
• Cellular location: Cytoplasm : P54651
• Total number of polymer chains: 1
• Total formula weight: 29496.21

Authors

Raman, S.,Suguna, K. (deposition date: 2015-01-12, release date: 2015-12-09, Last modification date: 2023-11-08)

Primary citation

Raman, S.,Singh, M.,Tatu, U.,Suguna, K.
First Structural View of a Peptide Interacting with the Nucleotide Binding Domain of Heat Shock Protein 90
Sci Rep, 5:17015-17015, 2015

PubMed Abstract: 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.

PubMed: 26599366
DOI: 10.1038/srep17015

Experimental method

X-RAY DIFFRACTION (2.455 Å)