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Argonne scientists determine structure of staph, anthrax enzyme

Researchers at the U.S. Department of Energy's Argonne National Laboratory and the University of Chicago have determined the crystal structure of sortase B, an enzyme found in the bacteria that cause staph and anthrax. While an antibiotic is probably five to seven years away, the structure could provide the first clue in developing a treatment for the infections.

The research is published today in the journal Structure.

It took the researchers 21 days to build the three dimensional model of sortase from the genome. Without the new technology available at Argonne's Structural Biology Center, including the Advanced Photon Source's powerful X-rays to illuminate the structures and the Midwest Center for Structural Genomics' robotic and automation facilities for protein expression, purification and crystallization, the process could have taken several months.

By analyzing genomes, the researchers uncover information that will lead to structure-based or "rational" drug design. The problem is that researchers don't know what half the proteins coded by the genome do or how they work.

Now that the researchers understand the enzyme, they hope to find a way to stop it or at least to slow it down. Sortase attaches proteins to the surface of bacterial pathogens. These proteins help the pathogens survive and flourish.

Bacteria like staph and anthrax need iron to function. But little free iron is available in the blood stream because most of it is bound in red blood cells. So the bacteria develop a mechanism to pry open the red blood cells, and these proteins help them.

"This is actually a very smart mechanism," said Andreji Joachimiak, lead researcher and director of the Structural Biology Center. The process is outlined in an article published in Science last year by Olaf Schneewind of the University of Chicago, which laid the groundwork for the sortase project.

The bacteria open the blood cell, bind the hemoglobin that contains heme
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Contact: Beth Quill
media@anl.gov
630-252-5549
DOE/Argonne National Laboratory
14-Jul-2004


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