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Researchers view protein's structural changes in real time

HOUSTON Dramatic structural changes that take place inside a protein in less than a billionth of a second have been filmed in high resolution with X-ray crystallography, enabling scientists to view them like a movie.

The ability to watch a protein functioning on the inside may lead to a better understanding of how it works, enabling scientists to engineer improved proteins for blood substitutes and improved treatments for genetic diseases.

Researchers at the National Institutes of Health (NIH), Rice University and the European Synchrotron Radiation Facility (ESRF) in France collaborated on the study, which is published in the June 20 issue of the journal Science.

Philip Anfinrud, senior biomedical research scientist in the Laboratory of Chemical Physics at the NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), headed the study of the protein myoglobin, which provides oxygen to muscles when they contract.

The scientists aimed a laser pulse at the protein for a trillionth of a second to break the chemical bond that links carbon monoxide to the protein. Noting the time when this reaction began, the scientists then used X-ray crystallography to take snapshots of the protein's structure, starting at one 10-billionth of a second. By stitching together the series of still images, the researchers created a moving picture of the changes taking place within the protein.

"The movie shows quite clearly the structural changes that contribute to the efficient expulsion of the toxic carbon monoxide from the protein," Anfinrud said.

For the study, the researchers used a mutant of myoglobin developed in the lab of John Olson at Rice, because in this variant of the protein, the rate at which carbon monoxide is swept away from the binding site is sped up by 1,000 times. Carbon monoxide, a toxic gas molecule, was used instead of oxygen because the protein-carbon monoxide complex is more stable and can endure
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Contact: B.J. Almond
balmond@rice.edu
713-348-6770
Rice University
19-Jun-2003


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