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No More Business as Usual for Public Structural Genomics Effort, Rockefeller Scientist Says

PHILADELPHIA, May 15 - With the right funding and oversight, academic scientists could determine the structures of all protein folds within five years, Stephen Burley, the principal investigator of the New York Structural Genomics Research Consortium, said Tuesday.

Burley, a molecular biophysicist at Rockefeller University, told GenomeWeb that structural biologists have a duty to the larger life science community to determine every protein shape as quickly as possible.

"If we wait for 'business as usual' it will take us 10 to 20 years to fill the universe of all protein structures," Burley said during a break in a proteomics conference. "[But] if we have an organized, concerted, and well funded effort we'll get there much much faster. I think we'll get there within 5 years."

Last September, Burley's consortium became one of seven regional centers to receive funding from the National Institute of General Medical Sciences, a division of NIH, as part of a public effort to elucidate protein structures. In April, NIGMS said it would fund an additional three such centers, as part of the five-year, $150 million initiative.

Unlike private efforts to determine the structures of only those proteins with direct medical relevance, the publicly-funded centers are focusing on families of proteins that participate in general cellular pathways, beginning with pathways found in model organisms such as the fruifly, nematode, and E. coli , Burley said.

But rather than find the structure of each of the estimated 300,000 to one million proteins found in eukaryotic cells, the NIGMS-funded effort will take a more step-wise approach.

Academic structural biologists will first concentrate their efforts on using x-ray crystallography to find the structure of all protein folds--the 2,000 to 5,000 structural elements that are put together in different combinations to make up a protein. Then, Burley and other academic scientists plan to resolve the structure of one protein in each of the estimated 30,000 protein families, or groups of proteins with similar three-dimensional structure.

While finding the structure of most protein folds will take less than five years, Burley said, determining the structures of the 30,000 protein families will most likely take five to ten years.

Once the publicly-funded effort has resolved the general structures of these 30,000 families, other investigators, including private companies, could delve more deeply into the proteins' structures to find how certain proteins could be used therapeutically, said Burley.

"Maybe there are particular proteins that act as drug targets where somebody would go back and do a structure," he said. "But they would be greatly helped by the fact that they already knew what [the protein family] looked like."

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