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Structure determined for critical SARS enzyme

DOE/Argonne National Laboratory : 08 April, 2007  (Technical Article)
Moving one step closer in the battle against Severe Acute Respiratory Syndrome, researchers from a California company using the powerful X-rays at the Advanced Photon Source have determined the first structure of the main protease from the coronavirus that causes SARS. A protease is a viral enzyme critical in the SARS life cycle.
The scientists from Structural GenomiX created a three-dimensional, high-resolution image of a crystal of the SARS virus, which will be useful to researchers developing a drug to inhibit the SARS virus replication. A similar strategy succeeded with the human immunodeficiency virus protease for treatment of AIDS.

Structural GenomiX is a San Diego, Calif., -based company that operates a macromolecular X-ray diffraction beamline at the APS, located at the U.S. Department of Energy's Argonne National Laboratory. The APS is this hemisphere's most brilliant source of X-rays for research. The company uses the X-rays to reveal in atomic detail how small molecules interact with drug targets in structure-guided drug design.

Because of the serious public health issue posed by SARS, Structural GenomiX deposited the crystal structure in the Protein Data Bank, a public database available to researchers worldwide, before publishing a paper in a refereed scientific journal. The company is exploring collaborative opportunities to develop a treatment.

With the experimental structure and an ample supply of crystals of the SARS main protease in hand, the company can now conduct experiments to determine the structure of the site where the protease creates infectious particles, the protease-inhibitor complex, and to create a drug molecule that fits in the active site to block this step.

Structural GenomiX used its proprietary process to create the crystal and the company's X-ray data collection facility at the APS to determine the protease's crystal structure at a resolution of 1.86 Angstroms, less than one atom's width.

They determined the crystal structure in a little more than one month after receiving cDNA clones from the Genome Institute of Singapore. The typical timeframe for this is usually months or years.

'SARS has been labeled the first '21st century epidemic',' said Joshua Lederberg, Ph.D., President Emeritus of The Rockefeller University, Nobel Laureate, and a leading expert in antiviral research.

Structural GenomiX is setting an example by sharing this structure with the research world to speed drug development in case SARS recurs, Lederberg said.
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