Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UH physicists study behavior of enzyme linked to Alzheimer's, cancer

22.11.2010
Results published in the journal Proceedings of the National Academy of Sciences

University of Houston (UH) physicists are using complex computer simulations to illuminate the workings of a crucial protein that, when malfunctioning, may cause Alzheimer's and cancer.

Margaret Cheung, assistant professor of physics at UH, and Antonios Samiotakis, a physics Ph.D. student, described their findings in a paper titled "Structure, function, and folding of phosphoglycerate kinase (PGK) are strongly perturbed by macromolecular crowding," published in a recent issue of the journal Proceedings of the National Academy of Sciences, one of the world's most-cited multidisciplinary scientific serials. The research was funded by a nearly $224,000 National Science Foundation grant in support of Samiotakis' dissertation.

"Imagine you're walking down the aisle toward an exit after a movie in a crowded theatre. The pace of your motion would be slowed down by the moving crowd and narrow space between the aisles. However, you can still maneuver your arm, stretch out and pat your friend on the shoulder who slept through the movie," Cheung said. "This can be the same environment inside a crowded cell from the viewpoint of a protein, the workhorse of all living systems. Proteins always 'talk' to each other inside cells, and they pass information about what happens to the cell and how to respond promptly. Failure to do so may cause uncontrollable cell growth that leads to cancer or cause malfunction of a cell that leads to Alzheimer's disease. Understanding a protein inside cells – in terms of structures and enzymatic activity – is important to shed light on preventing, managing or curing these diseases at a molecular level."

Cheung, a theoretical physicist, and Martin Gruebele, her experimental collaborator at the University of Illinois at Urbana-Champaign, led a team that unlocked this mystery. Studying the PGK enzyme, Cheung used computer models that simulate the environment inside a cell. Biochemists typically study proteins in water, but such test tube research is limited because it cannot gauge how a protein actually functions inside a crowded cell, where it can interact with DNA, ribosomes and other molecules.

The PGK enzyme plays a key role in the process of glycolysis, which is the metabolic breakdown of glucose and other sugars that releases energy in the form of ATP. ATP molecules are basically like packets of fuel that power biological molecular motors. This conversion of food to energy is present in every organism, from yeast to humans. Malfunction of the glycolytic pathway has been linked to Alzheimer's disease and cancer. Patients with reduced metabolic rates in the brain have been found to be at risk for Alzheimer's disease, while out-of-control metabolic rates are believed to fuel the growth of malignant tumor cells.

Scientists had previously believed that a PGK enzyme shaped like Pac-Man had to undergo a dynamic hinge motion to perform its metabolic function. However, in the computer models mimicking the cell interior, Cheung found that the enzyme was already functioning in its closed Pac-Man state in the jam-packed surrounding. In fact, the enzyme was 15 times more active in the tight spaces of a crowded cell. This shows that in cell-like conditions the function of a protein is more active and efficient than in a dilute condition, such as a test tube. This finding can drastically transform how scientists view proteins and their behavior when the environment of a cell is taken into account.

"This work deepens researchers' understanding of how proteins function, or don't function, in real cell conditions," Samiotakis said. "By understanding the impact of a crowded cell on the structure, dynamics of proteins can help researchers design efficient therapeutic means that will work better inside cells, with the goal to prevent diseases and improve human health."

Cheung and Samiotakis' computer simulations – performed using the supercomputers at the Texas Learning and Computation Center (TLC2) – were coupled with in vitro experiments by Gruebele and his team. Using the high-performance computing resources of TLC2 factored significantly in the success of their work.

"Picture having a type of medicine that can precisely recognize and target a key that causes Alzheimer's or cancer inside a crowded cell. Envision, then, the ability to switch a sick cell like this back to its healthy form of interaction at a molecular level," Cheung said. "This may become a reality in the near future. Our lab at UH is working toward that vision."

A copy of the article is available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955104/. A video produced by TLC2 that depicts PGK in the crowded environment inside cells is available at http://vimeo.com/15969373.

NOTE TO JOURNALISTS: Media may contact Lisa Merkl for high-resolution illustrations of the different characteristic PGK structures observed in the simulations.

About the University of Houston

The University of Houston is a comprehensive national research institution serving the globally competitive Houston and Gulf Coast Region by providing world-class faculty, experiential learning and strategic industry partnerships. UH serves more than 38,500 students in the nation's fourth-largest city, located in the most ethnically and culturally diverse region of the country.

About the College of Natural Sciences and Mathematics

The UH College of Natural Sciences and Mathematics, with 181 ranked faculty and approximately 4,500 students, offers bachelor's, master's and doctoral degrees in the natural sciences, computational sciences and mathematics. Faculty members in the departments of biology and biochemistry, chemistry, computer science, earth and atmospheric sciences, mathematics and physics conduct internationally recognized research in collaboration with industry, Texas Medical Center institutions, NASA and others worldwide.

For more information about UH, visit the university's Newsroom at http://www.uh.edu/news-events/.

To receive UH science news via e-mail, visit http://www.uh.edu/news-events/mailing-lists/sciencelistserv/index.php.

For additional news alerts about UH, follow us on Facebook at http://www.facebook.com/UHNewsEvents and Twitter at http://twitter.com/UH_News

Lisa Merkl | EurekAlert!
Further information:
http://www.uh.edu

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton 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: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>