Scientists determine structure of staph, anthrax enzyme

Researchers at Argonne and the University of Chicago have determined the crystal structure of sortase B, an enzyme found in the bacteria that cause staph infections 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 was published 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.

Sortase would be a good target for a drug, because if one can block the enzyme, it will not be able to attach these proteins to the surface and the bacteria would not be able to get iron from our bloodstream.

The research looks at sortase from both staph and anthrax — more formally, Staphylococcus aureus and Bacillus anthracis, and concludes that the two are similar.

Now that the structure is known, the next step is to mimic the signal sequence, or peptide, in the protein with a drug that blocks the enzyme.

This step is based primarily on trial and error. However, if scientists know the structure, they can make a more educated guess.

Research on this and other projects continues at Argonne's Structural Biology Center, where more than 530 structures have been determined. Nearly 150 protein structures have been determined at the Midwest Center for Structural Genomics and recorded with the International Protein Data Bank — that's more than any other structural genomics center.

The published research was supported by the National Institutes of Health Grants and the U.S. Department of Energy Office of Biological and Environmental Research.