NASA Research Helps Map Protein Structures — Key in the Development of New Disease-Fighting Drugs
Space- and ground-based studies conducted by NASA-sponsored scientists are providing a better understanding of protein structures and functions. Determining the structures of proteins -- which allow living organisms to function -- is essential to the future design of new, more effective drugs against diseases such as AIDS, heart disease, cancer, diabetes, sickle-cell anemia, hepatitis and rheumatoid arthritis.
While ground-based research has been (historically) vital to the discovery of protein structures, in the near-zero gravity environment of space researchers have produced some of the largest, highest-quality protein crystals ever, which is critical for pharmaceutical research. On Earth, the influence of gravity can interfere with the crystal growth process, and this can lead to structural imperfections and poor information.
"At least sixty percent of all protein crystals flown in space produce sufficient overall quality and size to be X-rayed for three-dimensional structure analysis," said Dr. Larry DeLucas, director of the Center for Macromolecular Crystallography at the University of Alabama at Birmingham. "Twenty five percent of the proteins we fly in space produce the best crystallographic data when compared to their earth-grown counterparts."
Already, more than 15 protein structures have been determined from protein crystal growth research, and these findings are being used to improve our knowledge of protein structures.
Some of the space research done with protein crystals that would not have been possible on Earth includes:
Through NASA-funded protein crystal growth research, scientists have made an important step toward developing a treatment for Respiratory Syncytial Virus -- a life-threatening virus that causes pneumonia and severe upper respiratory infection in infants and young children. Investigators have determined the structure of a potentially important therapeutic antibody to the disease. This knowledge will permit scientists to understand key interactions between the antibody and the virus, facilitating development of treatments for the disease.
Factor D protein crystals -- successfully grown in space -- led to development of a drug that may aid patients recovering from open heart surgery. The promising drug, designed to inhibit the human body's inflammatory responses to open heart surgery, is due to begin human clinical testing this year.
Detailed pictures of insulin proteins -- mapped from space-grown crystals -- will add information for the development of new therapeutic insulin treatments for the control of diabetes. Such treatments would greatly improve the quality of life of people on insulin therapy by reducing the number of injections they require. It also would reduce the cost of treatment, which accounts for one-seventh of the nation's health care costs.
A protein crystal growth study conducted during a recent Space Shuttle flight obtained important results about antithrombin -- a protein which controls blood coagulation in human plasma. Successful crystal growth in space made it possible to further define the molecular structure of the protein and how it works in the human body, which has important implications for medicine.
A space-based study of the HIV protease/inhibitor complex resulted in improved resolution of the protein's structure. Results may have applications for designing new drugs for AIDS therapies.
Neuraminidase is a target for the treatment and prevention of the flu. Influenza protein crystals from several Space Shuttle flights had a significant impact on the progress for a flu medicine. As a result, several potent inhibitors of viral influenza (types A and B) have been developed and it is anticipated that phase I human clinical trials will begin this year.
Experiments in protein crystallization research have yielded detailed structural data on proteins associated with Chagas' disease, a debilitating and deadly disease that affects more than 20 million people in Latin America and parts of the United States.
"These experiments have provided persuasive evidence that growth in microgravity can produce crystals of larger size, better shape and higher quality than have been obtained on Earth," according to a 1995 report issued by the National Research Council in Washington, D.C. "They also show that benefits from microgravity crystal growth can be crucial to success in protein structure determination."
BioCryst Pharmaceuticals Inc. in Birmingham, Ala.; New Century Pharmaceuticals in Huntsville, Ala.; Parke-Davis in Ann Arbor, Mich.; DuPont Merck Pharmaceutical Company in Wilmington, Del.; the Upjohn Company in Kalamazoo, Mich.; and Eli Lilly & Company in Indianapolis, Ind., are among the 20 companies working with NASA as industry partners in the research of protein crystal structures. More than 85 investigators representing industry and academic affiliates have conducted protein studies in space, resulting in important information needed to help resolve health challenges both in America and other countries around the world.
For More Information
To arrange interviews with NASA managers of Marshall's Microgravity Research Program Office, contact Steve Roy of Marshall's Media Relations Office at (256) 544-0034.
For more information on protein crystal growth research, visit the Marshall Space Flight Center at: