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Elucidation of the Hsp90 C-terminal inhibitor binding site.

ABSTRACT: The Hsp90 chaperone machine is required for the folding, activation, and/or stabilization of more than 50 proteins directly related to malignant progression. Hsp90 contains small molecule binding sites at both its N- and C-terminal domains; however, limited structural and biochemical data regarding the C-terminal binding site is available. In this report, the small molecule binding site in the Hsp90 C-terminal domain was revealed by protease fingerprinting and photoaffinity labeling utilizing LC-MS/MS. The identified site was characterized by generation of a homology model for hHsp90? using the SAXS open structure of HtpG and docking the bioactive conformation of NB into the generated model. The resulting model for the bioactive conformation of NB bound to Hsp90? is presented herein.

SUBMITTER: Matts RL

PROVIDER: S-EPMC3164513 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Elucidation of the Hsp90 C-terminal inhibitor binding site.

Matts Robert L RL Dixit Anshuman A Peterson Laura B LB Sun Liang L Voruganti Sudhakar S Kalyanaraman Palgunan P Hartson Steve D SD Verkhivker Gennady M GM Blagg Brian S J BS

ACS chemical biology 20110517 8

The Hsp90 chaperone machine is required for the folding, activation, and/or stabilization of more than 50 proteins directly related to malignant progression. Hsp90 contains small molecule binding sites at both its N- and C-terminal domains; however, limited structural and biochemical data regarding the C-terminal binding site is available. In this report, the small molecule binding site in the Hsp90 C-terminal domain was revealed by protease fingerprinting and photoaffinity labeling utilizing LC ...[more]

PMID: 21548602

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