First high-res 3D structures of mammalian HSP90 prot...(iversity at Buffalo which is housed at t...)

Why Is This Important?

This is groundbreaking work for a number of reasons: It is the first high resolution picture of any member of the hsp90 family. High resolution is needed for a detailed understanding of protein function. It is also the first structure of a mammalian member of the hsp90 family. This is important since drugs and other therapeutics need to be developed for human use, and thus must target the mammalian protein. Finally, the work shows for the first time how members of the hsp90 family of chaperone proteins can differ from each other, while still being part of the same overall family.

Scientific Understanding

The mammalian member of this protein family is different than those previously studied which were solved from either bacteria or yeast. Human energy production and consumption rates are more similar to those found in the GRP94 proteins than to the more widely studied HSP90 proteins. This means that the insights gained by a greater scientific understanding of how GRP94 works will have more direct applications to human diseases.

Medical Implications and Drug Development

Inhibitors currently are being designed for HSP90 in an attempt to treat the diseases in which HSP90 plays a role. However, these are broad-spectrum inhibitors of all HSP90s which means that unwanted side effects may occur. The Gewirth labs work clarifies GRP94s place in this family and has already stimulated interest in this chaperone as a drug target. This understanding would allow for the long-term development of a family of drugs that could be narrowly targeted for individual proteins, for example specifically treating sepsis only.

Economic Impact

Just as companies have been founded to develop HSP90 inhibitors, the same potential exists here. This will spur a new line of inquiry into GRP94.
'/>"/>