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First High-Res 3-D Structures of Mammalian HSP90 Protein Solved, Key to Better Targets for AIDS, Sepsis, Cancer Drugs
Date:10/19/2007

HWI Scientist Dr. Dan Gewirth's Groundbreaking Research Makes Cover of

Molecular Cell

BUFFALO, N.Y., Oct. 19 /PRNewswire/ -- Dr. Dan Gewirth, Hauptman-Woodward senior research scientist, has just solved the structure of the first mammalian GRP94 protein implicated in immune diseases such as sepsis, AIDS and certain cancers. His work is being published today in a cover article in a top scientific journal -- Molecular Cell.

Gewirth's study confirms his 2001 hypothesis that this protein -- GRP94 -- is from the same family as the better known HSP90 proteins. As ligand-regulated chaperones -- proteins that help other cellular proteins achieve their active shapes, the HSP90s are key players in cellular regulation and recognition. The HSP90 proteins have been the subject of increasing international interest as scientists have discovered that they can be targeted therapeutically with drugs that lead to either stimulation as well as inhibition. For example, inhibitors of HSP90s are being developed as therapies for diseases ranging from cancer to sepsis, and drugs that stimulate HSP90 action may be appropriate therapies for diseases involving protein folding, such as cystic fibrosis, prion diseases, and Alzheimer's Disease.

Since 2001, Gewirth and his lab have been using the technique of X-ray diffraction to solve the first high-resolution structure of this protein from mammalian origins, to understand its function and to determine if it is indeed a member of the HSP90 family of proteins. The structure and activity patterns of this protein prove conclusively that this is indeed a member of the same family.

"Our work opens the door to a more intensive evaluation of this protein both from a mechanistic as well as a therapeutic point of view. In addition to aiding our understanding of the fundamental biology of chaperone-mediated protein folding, this work lays the foundation for the design of drugs that specificall
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SOURCE Hauptman-Woodward Medical Research Institute
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