Brookhaven Lab & Battelle collaborate on research that may lead to novel anti-microbial drugs

UPTON, NY The U.S. Department of Energy's Brookhaven National Laboratory and Battelle of Columbus, Ohio, have joined together in a Cooperative Research and Development Agreement (CRADA) to determine the structures of microbial proteins, research that may lead to the design of novel anti-microbial drugs. These drugs would be able to stop fungal or bacterial infections in patients whose immune systems are compromised, such as those with cancer or AIDS, or patients undergoing immunosuppressive therapies for organ transplantation or for the treatment of diseases such as multiple sclerosis and psoriasis.

As a first step in reaching this goal of developing new drugs, Brookhaven biologist Maria Bewley will use the National Synchrotron Light Source (NSLS) at Brookhaven to determine the structures of three proteins that are found in the metabolic pathways, or sequence of reactions catalyzed by enzymes, that enable lysine to be synthesized by microbes. Lysine is one of eight essential amino acids that humans must consume because they cannot synthesize it.

Fungi and bacteria have pathways that can synthesize lysine. The enzymes in these pathways are ideal targets for developing anti-microbial drugs, since they are absent in humans.

"We can kill fungi and bacteria if we can develop a drug that can block the enzymes in their pathways before they synthesize lysine," Bewley explained. "Since these drugs would attack enzymes that don't exist in humans, it is unlikely that they would have negative effects in the human body."

Designing such drugs, however, is hampered by the lack of structural information about the three enzymes in the lysine pathways. To obtain structural information on them, Bewley will clone and express each of the enzymes using a patented gene expression system, known as T-7, invented by Brookhaven biologists. Then she will purify each enzyme, crystallize it, and expose it to x-rays at the NSLS. A detector records a pattern from

Contact: Diane Greenberg
DOE/Brookhaven National Laboratory

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