Scientists funded by the National Institute of General Medical Sciences (NIGMS) have snapped a molecular picture of the tether that anthrax- and staph-causing bacteria use to hook onto human red blood cells. The tether, an enzyme called sortase B, allows the bacteria to rob the cells of iron, which they need to survive.
The researchers took a mere three weeks to solve the high-resolution crystal structure of the sortase B protein, a process that normally takes several months or longer to complete.
The work is part of the NIGMS Protein Structure Initiative (PSI), a federal, university, and industry effort aimed at dramatically reducing the costs and lessening the time it takes to determine a three-dimensional protein structure. The long-range goal of the PSI is to make the structures of most proteins easily obtainable from knowledge of their corresponding DNA sequences.
"This study beautifully illustrates how determining a protein's structure can shed light on its function and lead to important medical insights," said Jeremy M. Berg, Ph.D., NIGMS director. "It also demonstrates how ramping up technology can help scientists with creative ideas get their work done very rapidly."
Structural biologist Andrzej Joachimiak, Ph.D., who directs the PSI's Midwest Center for Structural Genomics at Argonne National Laboratory in Illinois, led the research, which is reported in the July 2004 issue of the journal Structure.
"Joachimiak's findings are an example of the payoffs of the PSI's automated, high-throughput approaches to solving protein structures," said PSI director John Norvell, Ph.D. "By providing access to state-of-the-art robotic devices and facilities for sample preparation, the PSI enables researchers to work very efficiently and productively."
The scientists hope to use their knowledge of sortase B's structure to rationally design new antibiotics that would nip dangerous bacteria in the bud, before they have a chance to cause infections. Staph is responsible for a range of health problems including skin infections and food poisoning, and anthrax infection can be life-threatening.
For more information about the PSI, see http://www.nigms.nih.gov/Initiatives/PSI/.
NIGMS supports basic biomedical research that lays the foundation for advances in disease diagnosis, treatment, and prevention. It is part of the National Institutes of Health, U.S. Department of Health and Human Services.
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Reference: Zhang R, Wu R, Joachimiak G, Mazmanian SK, Missiakas DM, Gornicki P, Schneewind O, Joachimiak A. Structures of Sortase B from Staphylococcus aureus and Bacillus anthracis Reveal Catalytic Amino Acid Triad in the Active Site. Structure 12:1147-56, 2004.
To arrange an interview with an NIGMS scientist, contact the NIGMS Office of Communications and Public Liaison at 301-496-7301 or info@nigms.nih.gov.
