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Structural Genomix Publishes Structures of Protein Involved in Bacterial Pathway

NEW YORK, June 6 - Scientists at Structural Genomix published the structures of three proteins associated with bacterial virulence in Wednesday's issue of the journal Structure, providing a detailed example of the company's approach to solving protein structures and incrementally advancing research into antibacterial drugs, scientists familiar with the paper said.

The protein structures, of the protein LuxS in three different forms, or orthologs, are important because they are involved in a pathway that allows virulent bacteria to sense the density of cells surrounding them, a pathway called quorum sensing, said Mike Milburn, vice president for structural biology at Structural Genomix. Knowing the protein's structure, he said, could allow scientists to design drugs that make the bacteria think there aren't enough surrounding cells for the bacteria to live off, causing the organism to die.

Determining the protein structure using x-ray crystallography first required Structural Genomix scientists to produce the protein in a form that would crystallize. To do this, the team, led by Hal Lewis, a scientist at Structural Genomix, expressed the protein in five different bacterial species to increase the probability that one or more of the expressed proteins would crystallize in a suitable form for x-ray crystallography, Milburn said. In fact, three of the proteins crystallized.

"We felt this was a fairly powerful scientific story of Structural Genomix' approach for determining protein structures using a high-throughput platform," said Milburn. "We had a great deal of scientific information because we studied the proteins from three species."

Other scientists, however, said that while the protein structures are important, the approach outlined in the paper is not necessarily novel, and that many other groups are working on the quorum-sensing pathway as well.

"Structure-assisted drug design certainly is a valid approach [for developing drugs]," said Jeffery Stein, chief scientific officer at Quorex Pharmaceuticals, a company in Carlsbad, Calif., focusing on developing drugs that target the quorum-sensing pathway. But Stein added that the approach for investigating the protein's active site "is being used by many other groups as well," he said.

Others were more enthusiastic about the recent contribution.

"[This] is an extremely important pathway in microbial pathogenesis," said Bonnie Bassler, a molecular biologist at Princeton University who is familiar with the research. "Structural Genomix is adding another piece to the puzzle to what's being worked by a number of different people."

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