Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Model of enzyme's structure could spur new therapies

07.11.2011
MAP kinase resolved well enough to spot potentially unique drug target

In many pharmaceutical company and university laboratories, scientists are looking closely at kinase complexes because the enzymes play key roles in essential cell functions.

By taking unusual steps to examine a kinase complex, researchers at Brown University and the National Institutes of Health have found a sought-after prize: an unprecedentedly detailed description of its structure complete with a rare location on its structure that could be a target for new therapeutic drugs.

"Disregulation always leads to disease," said Wolfgang Peti, associate professor of medicine and chemistry at Brown University and senior author of a paper published online Nov. 6 in Nature Chemical Biology. "To make better drugs, what we want to do is look for individual things that are different between different complexes. The problem is we didn't know where those non-common spots are. We didn't have the structures that tell us the story. We were the first to get one of those structures."

The complex that Peti, Brown colleague Rebecca Page, and their team has now characterized is hardly a household name: p38alpha:HePTP. It does however, matter in millions of households around the world. It is a member of the MAP kinase family, enzymes that regulate cell functions such as growth and inflammation. Diseases that correlate with disruptions to MAP kinase signaling include Alzheimer's disease, rheumatoid arthritis, and cancer.

To determine the structure, the group took the rare step of combining techniques including nuclear magnetic resonance spectroscopy and small-angle X-ray scattering, using the National Synchrotron Light Source at Brookhaven National Laboratory on Long Island. The result was the clearest picture yet of a MAP kinase complex, which turns out to measure a mere 108 Angstroms (tenths of billionths of a meter) long by 30 Angstroms wide. The resolution of their resulting model is on the scale of individual atoms.

To elucidate their model, they probed the complex to discover areas where p38alpha binds to different HePTP-derived peptides. They found a specific area called "KIS" that is responsible for how the p38alpha:HePTP complex forms in its unique way.

"That really showed there are these areas outside the common sites that are likely unique between different complexes," Peti said.

The next step is to learn more about KIS and the role it could ultimately play in disregulation and disease. In their paper, the authors expressed optimism that their newfound knowledge will have clinical relevance: "These results provide novel insights into the molecular interactions that regulate the strength and duration of MAP kinase signaling and, in turn, provide novel avenues for therapeutic interventions of MAP kinase-related diseases."

In addition to Peti and Page, other Brown authors include lead author Dana Francis and co-author Dorothy Koveal. Authors from the National Institute of Diabetes and Digestive and Kidney Diseases were Bartosz Rozycki and Gerhard Hummer.

The American Cancer Society funded the research.

David Orenstein | EurekAlert!
Further information:
http://www.brown.edu

More articles from Life Sciences:

nachricht Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology

nachricht Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Osaka university researchers make the slipperiest surfaces adhesive

18.10.2017 | Materials Sciences

Space radiation won't stop NASA's human exploration

18.10.2017 | Physics and Astronomy

Los Alamos researchers and supercomputers help interpret the latest LIGO findings

18.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>