Scientists find donut-shaped structure of enzyme involved in energy metabolism

Feb 16, 2010
In humans, proline is important for suppression of cancer, cell death and oxidation. Understanding the structure of this enzyme will help scientists better understand how it functions and develop drugs that may inhibit its catalytic function. Credit: Photo courtesy of MU News Bureau.

If subway terminals didn't exist and people had to exit subway stations to switch subway lines, transit time would increase. People also may encounter distractions, such as grabbing a cup of coffee, instead of getting on the other line. Molecules also use "terminals" to save transit time during enzyme-catalyzed processes.

Using advanced X-radiation techniques, University of Missouri researchers were able to visualize one of these terminals inside of an enzyme that degrades proline, which is an amino acid that has a central role in metabolism. In humans, proline is important for suppression of cancer, cell death and oxidation. Understanding the structure of this enzyme will help scientists better understand how it functions and develop drugs that may inhibit its catalytic function.

"This is an aesthetically interesting enzyme that resembles a donut-shaped ring," said John Tanner, professor in the Department of Chemistry and the Department of Biochemistry. "Hidden under the surface of the protein is a system of tunnels and rooms - like a subway system for molecules. The purpose of this system is to provide an interior passageway connecting the two catalytic sites of the enzyme. The movement of reactant molecules through this passageway is known as channeling, which makes enzymes efficient by isolating the reactants from other enzymatic reactions. Channeling potentially allows for decreased transit time between catalytic sites and protection from competing enzymatic reactions. The reactions occur without the reactants ever leaving the confines of the protein, which is efficient."

In the study, several proline-degrading proteins were screened for their ability to crystallize. A crystal is needed in order to perform experiments, which provide high resolution images of the protein's three-dimensional structure. Additional studies using small-angle X-ray scattering and centrifugation provided crucial information about the protein's donut shape. These techniques help researchers determine the structure and composition of the enzyme.

"The complementary methods of the X-ray crystallography, small-angle X-ray scattering, and centrifugation gave us a whole picture of the structure of the enzyme," Tanner said. "Knowing the structure of the enzyme helps us understand the function of the enzyme. Once we know an enzyme's structure, we can begin to interpret other important data, such as the enzyme's role in specific reactions, how its activity is controlled and how a drug could inhibit the ."

The study, "Crystal structure of the bifunctional Proline utilization A flavoenzyme from Bradyrhizobium japonicum," was published in Proceedings of the National Academy of Sciences this month.

Explore further: Jumping hurdles in the RNA world

Related Stories

Unlocking the function of enzymes

Nov 06, 2007

Fitting a key into a lock may seem like a simple task, but researchers at Texas A&M University are using a method that involves testing thousands of keys to unlock the functions of enzymes, and their findings could open the ...

Study reveals the regulatory mechanism of key enzyme

Sep 20, 2007

Research conducted at the University of California, San Diego (UCSD) School of Medicine has shed new light on the structure and function of one of the key proteins in all mammalian cells, protein kinase A ...

Recommended for you

Molecules that came in handy for first life on Earth

46 minutes ago

For the first time, chemists have successfully produced amino acid-like molecules that all have the same 'handedness', from simple building blocks and in a single test tube. Could this be how life started. ...

Jumping hurdles in the RNA world

Nov 21, 2014

Astrobiologists have shown that the formation of RNA from prebiotic reactions may not be as problematic as scientists once thought.

New computer model sets new precedent in drug discovery

Nov 18, 2014

A major challenge faced by the pharmaceutical industry has been how to rationally design and select protein molecules to create effective biologic drug therapies while reducing unintended side effects - a challenge that has ...

Finding new ways to make drugs

Nov 18, 2014

Chemists have developed a revolutionary new way to manufacture natural chemicals and used it to assemble a scarce anti-inflammatory drug with potential to treat cancer and malaria.

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

callywally
not rated yet Feb 16, 2010
Speaking as a layman on the subject, I'd love to see an animation or principle sketches of the action taking place within this protein.

A question: We have folding@home.. shouldn't we be able to solve the folded 3d structure if we know the molecule's 1D structure? Another question regarding folding: Can I think of protein building as a piece-by-piece 1-dimensional puzzle, so the protein 'string' is exreted from the cell machinery in a way which makes the first parts of the protein fold before the rest of the protein is assembled? Wouldn't that profoundly influence or guide the protein folding?

Sorry, uh questions popping up while typing..

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.