Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

First high-res 3D structures of mammalian HSP90 protein solved

16.10.2007
Key to better targets for AIDS, sepsis, cancer drugs

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.

... more about:
»GRP94 »Gewirth »Hsp90 »Protein »Sepsis »mammalian

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 specifically target individual members of the hsp90 family” Gewirth, who also holds a post as an associate professor in the Structural Biology department of the University at Buffalo which is housed at the Hauptman-Woodward Medical Research Institute, said.

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 lab’s work clarifies GRP94’s 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. While this work is its infancy, medicinal chemists will be interested in developing GRP94-targeted drugs,” Gewirth said.

Tara A. Ellis | EurekAlert!
Further information:
http://www.hwi.buffalo.edu

Further reports about: GRP94 Gewirth Hsp90 Protein Sepsis mammalian

More articles from Life Sciences:

nachricht Molecular Force Sensors
20.09.2017 | Max-Planck-Institut für Biochemie

nachricht Foster tadpoles trigger parental instinct in poison frogs
20.09.2017 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

Im Focus: Silencing bacteria

HZI researchers pave the way for new agents that render hospital pathogens mute

Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Molecular Force Sensors

20.09.2017 | Life Sciences

Producing electricity during flight

20.09.2017 | Power and Electrical Engineering

Tiny lasers from a gallery of whispers

20.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>