Mechanistic studies of Sansalvamide A-amide: an allosteric modulator of Hsp90.
Herein we show that San A-amide, a structurally unique molecule, influences a subset of cancer-related pathways involving Hsp90. We show that San A-amide specifically binds to the N-middle domain of Hsp90 allosterically disrupts the binding of proteins thought to interact with the Hsp90 C-terminal domain, while having no effect on an N-terminal domain client protein. This unique mechanism suggests that San A-amide is a potential tool for studying C-terminal binding proteins of Hsp90 as well as a promising lead in the development of new cancer therapeutics.
Vasko
Robert C
RC
Department of Chemistry and Biochemistry, 5500 Campanile Road, San Diego State University, San Diego, CA 92182-1030.
Rodriguez
Rodrigo A
RA
Cunningham
Christian N
CN
Ardi
Veronica C
VC
Agard
David A
DA
McAlpine
Shelli R
SR