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BATON ROUGE -- The National Science Foundation and the National Institutes of Health have designated LSU's Center for Advanced Microstructures and Devices as a regional center for protein crystallography. When completed, CAMD will be the only such center within 1,000 miles.
The federal grant of nearly $2 million, jointly funded by NSF and NIH, will provide a new beamline to produce the colored x-ray light needed to determine protein shapes at CAMD, LSU's engine for generating highly focused x-ray light.
"I'm very happy this beamline is coming. It may well be the most important beamline at CAMD for the foreseeable future," said CAMD Director Josef Hormes.
Work on the beamline began five years ago after the then-director of CAMD, Volker Saille, and others attended a symposium on protein crystallography at Texas A&M. One of those others was the deputy director of CAMD, Ben Craft, who has guided the project through the many loops and twists of the funding process and is the principal investigator for the project at LSU.
The beamline is expected to be operational in two years.
The next closest center for protein crystallography is in Chicago; two more are in the Northeast, and the other two are in Northern California. Because of this, a number of universities and medical research centers are joining with LSU in this project. Rice University, the Baylor College of Medicine, the University of Houston, Texas A & M, the University of Oklahoma Medical Research Foundation and the University of Texas Medical Branch at Galveston all support the project and will be using the beamline.
The grant will also buy the special x-ray camera necessary to capture the results for analysis, said recent CAMD interim director Erwin Poliakoff.
"X-ray protein crystallography is a huge and growing field right now," Poliakoff said.
"This grant will make CAMD a player in this important area," said Lynn Jelinski, vice-chancellor for research and graduate studies.
Protein crystallography is an aspect of structural biology that is of interest to everyone from pharmaceutical companies that design drugs to medical researchers who want to know how and why things work the way they do, Poliakoff said.
"Biomolecules work like a lock-and-key mechanism. You have to know what the lock looks like before you can design a key for it. The proteins determine the structure of the locks, and they allow us to design better biological keys," he said.
The new beamline will allow researchers to shoot a beam of synchrotron light at a protein which has been crystallized like a piece of rock candy. As the light beam hits the internal structure of the molecule, it is deflected and flies out the other side at an angle. By rotating the specimen and by changing the color of the x-ray light, different angles are produced. The way the light scatters is captured by the camera. Scientists can then analyze the patterns produced by the scattered light and reconstruct an image of the protein.
The great advantage offered by CAMD is the high resolution of the images it can produce. Grover Waldrop, an assistant professor of biological sciences at LSU, compared images of proteins produced with synchrotron radiation to paintings by a realist painter. "With CAMD we will be able to get down to a single atom," he said. Images produced in other ways are more like paintings by Picasso, he said -- you know what's there, but it's harder to interpret.
Waldrop said that knowing the shape of proteins is critical to an understanding of the basic biological mechanisms of living things. "DNA is the blueprint, but it's proteins that do all the work. Each human being is what our proteins make us."
Proteins are long molecules made up of combinations of the 20 amino acids. The molecular string is not straight but is bunched up like a rubber band that has been twisted then relaxed. In the twists and folds of this bunched-up protein are "active sites," which attract chemical groups, such as simple sugars, from the surrounding environment and hold them in such a way that new compounds are formed. When the new compound is complete, the reaction that formed it releases it from the protein molecule, and the process begins again.
The key to making medicines is often in blocking these active sites, Waldrop said. "For instance, HIV protease is a protein that the human immunovirus needs to replicate. The HIV protease inhibitors that have been developed block the active sites on the HIV protease molecule and prevent the virus from replicating. If the virus doesn't replicate, it dies," he said.
According to a 1997 report by the Structural Biology Synchrotron Users Organization, synchrotron radiation study of proteins will have broad applications. In addition to aiding in the design of new drugs, it will help combat drug-resistant pathogens, such as the evolving forms of tuberculosis that are no longer controllable by available drugs; help find remedies for protozoan diseases, such as malaria and sleeping sickness; help design enzymes with which to degrade pollutants; and help create enzymes that are stable in industrial catalytic reactions.
Craft, whose field is nuclear physics, took a scientific overview of the project. "This project brings together science and technology ranging from special relativity to accelerator physics to biochemistry. The result is a microscope that allows scientists to identify the individual atoms and their locations within proteins," he said.
A center for the study of protein crystallography at LSU will also allow the university to recruit more faculty who are expert in this area. "This is the sort of thing that acts as a magnet for people who want to work in this field," Poliakoff said.
When the beamline is operational, researchers will be able to work about 100 experiments a year, which is a lot, Poliakoff said. Even so, the demand for such an experimental tool is so high that, if all goes well, CAMD may install another protein crystallography beamline five years down the line, he said.
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