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 Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>