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Breathing easy: LSU biochemists offer first 3-D model of asthma-causing inflammation enzyme
Date:2/2/2011

BATON ROUGE Inflammation is a healthy response in reaction to potentially harmful presences in the body. But when it starts in the lungs and builds up to a full-fledged asthma attack, it can be downright deadly. Chronic inflammation has been directly associated with heart disease and other physical ailments. But LSU graduate student Nathanial Gilbert and Professor of Biological Sciences Marcia Newcomer, together with Associate Professor Sue Bartlett, have developed the first 3-D model of Human 5-Lipoxygenase, or 5-LOX, the molecule responsible for creating inflammatory compounds that provoke asthma. This model will serve as a target for the design of new, more effective asthma medication.

Their research was printed in Science on Jan. 14 and was the subject of an article in Science Translational Medicine.

"This molecule is responsible for starting the synthesis of compounds referred to as 'signaling molecules,' which cause inflammation," said Newcomer. "If we can look at this molecule in closer detail than we have previously been able to do so, then that will allow for the development of better asthma medications that are able to stop an attack more effectively."

Prior to their development, scientists had been unable to study this molecule in detail because of its transient nature.

"It was really hard to work with," said Newcomer. "5-LOX is unstable. Before you could start your experiments, the enzyme would self-destruct."

The enzyme has an "Achilles' heel," which makes it prone to destabilization. But after working with another, hardier enzyme, Newcomer and her team were able to target the weak area, then bioengineer a replacement. Once they were able to apply this technique to 5-LOX, they were able to identify the complex pathway of how the molecule shuts itself off. The resulting molecule, complete with the engineered "heel," was then tested to verify that the output was precisely the same as its una
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Contact: Ashley Berthelot
aberth4@lsu.edu
225-578-3870
Louisiana State University
Source:Eurekalert

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