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UGA chemistry discovery could have major medical implications
Date:9/11/2012

Athens, Ga. The study of an oxygen-sensing bacterial regulatory protein by chemistry researchers at the University of Georgia has provided molecular insight into the oxygen sensing mechanism, which could ultimately lead to a better understanding of the ageing process and new treatments for human diseases such cancer, Parkinson's and Alzheimer's.

Michael Johnson, a distinguished research professor of chemistry in the UGA Franklin College of Arts and Sciences, and Bo Zhang, a UGA chemistry doctoral candidate, have discovered that the fumarate and nitrate reduction regulatory protein, or FNR, in E. coli senses oxygen by a new type of reversible structural change in an iron-sulfur cluster. The work was carried out in collaboration with Nick Le Brun and coworkers from the University of East Anglia. The results were published Sept. 10 in the journal Proceedings of the National Academy of Sciences USA.

Iron-sulfur clusters are abundant biological cofactors that play crucial roles in almost all of fundamental life processes, including respiration, photosynthesis, nitrogen fixation, DNA replication and repair. "Everyone has trillions of iron-sulfur clusters associated with enzymes and proteins in their bodies," Johnson said. "The problem is that they readily degrade in the presence of oxygen and other species that are associated with oxidative stress, leading to loss of protein function."

The research conducted at UGA and UEA focused on FNR, which senses the presence of oxygen in the environment and "switches" off and on specific genes in pathogens, such as E. coli, when there is no oxygen presentconditions often found in the human intestinal tract. Oxygen is sensed by FNR via its iron-sulfur clusterthat undergoes conversion from one form to another, smaller one, thereby causing the protein to change shapethe "switch"and leading to the turning off of genes associated with growth without oxygen.

"E. coli can decide what lif
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Contact: Michael K. Johnson
mkj@uga.edu
706-542-9378
University of Georgia
Source:Eurekalert

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