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 Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>