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Long-sought protein structure may help reveal how 'gene switch' works
Date:2/6/2009

GAITHERSBURG, Md.The bacterium behind one of mankind's deadliest scourges, tuberculosis, is helping researchers at the Commerce Department's National Institute of Standards and Technology (NIST) and the Department of Energy's Brookhaven National Laboratory (BNL) move closer to answering the decades-old question of what controls the switching on and off of genes that carry out all of life's functions.

In a Journal of Biological Chemistry paper* posted online this week, the NIST/BNL team reports that it has definedfor the first timethe structure of a "metabolic switch" found inside most types of bacteriathe cyclic AMP (cAMP) receptor protein, or CRPin its "off" state. CRP is the "binding site" (attachment point) for cAMP, a small molecule that, once attached, serves as the signal to throw the switch. This "on" state of CRP then turns on the genes that help a microbe survive in a human host.

The researchers hope that once the switching mechanism is understood the data can be used to develop new methods for preventing tuberculosis and other pathogenic bacterial diseases.

"We know that many pathogenic bacteria use cAMP as a signal for activating genes that keep the microbes thriving in adverse conditions, and therefore, remaining virulent," says NIST biochemist and lead author Travis Gallagher. "Blocking these processes might provide ways to shut down infections and save lives."

Additionally, the researchers believe that learning how this specific protein switch works may provide insight into how genes in general are regulated.

The biochemical puzzle surrounding the CRP switch is the mechanism by which the protein binds cAMP at one end, then attaches toand activatesa gene (DNA) at the other end. Believing that the protein somehow changes its overall shape after binding cAMP, researchers set out 25 years ago to study the structure of CRP in both its active state (with cAMP bound to it) and inactive state (wit
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Contact: Michael E. Newman
michael.newman@nist.gov
301-975-3025
National Institute of Standards and Technology (NIST)
Source:Eurekalert  

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