The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation.

Published

Journal Article

Many functions of the chaperone, heat shock protein 90 (hsp90), are inhibited by the drug geldanamycin that specifically binds hsp90. We have studied an amino-terminal domain of hsp90 whose crystal structure has recently been solved and determined to contain a geldanamycin-binding site. We demonstrate that, in solution, drug binding is exclusive to this domain. This domain also binds ATP linked to Sepharose through the gamma-phosphate. Binding is specific for ATP and ADP and is inhibited by geldanamycin. Mutation of four glycine residues within two proposed ATP binding motifs diminishes both geldanamycin binding and the ATP-dependent conversion of hsp90 to a conformation capable of binding the co-chaperone p23. Since p23 binding requires regions outside the 1-221 domain of hsp90, these results indicate a common site for nucleotides and geldanamycin that regulates the conformation of other hsp90 domains.

Full Text

Duke Authors

Cited Authors

  • Grenert, JP; Sullivan, WP; Fadden, P; Haystead, TA; Clark, J; Mimnaugh, E; Krutzsch, H; Ochel, HJ; Schulte, TW; Sausville, E; Neckers, LM; Toft, DO

Published Date

  • September 19, 1997

Published In

Volume / Issue

  • 272 / 38

Start / End Page

  • 23843 - 23850

PubMed ID

  • 9295332

Pubmed Central ID

  • 9295332

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.272.38.23843

Language

  • eng

Conference Location

  • United States