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Scientists unlock secrets of protein from disease-causing fungus

Posted on Thursday, May 01, 2014 · Volume: XLVII · Issue: 9


This illustration shows the crystal structure of the SOD5 protein from Candida albicans. It is superimposed on an image of the actual organism. C. albicans is the most common fungal pathogen to infect humans. Photo courtesy of P. John Hart, Ph.D.
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This illustration shows the crystal structure of the SOD5 protein from Candida albicans. It is superimposed on an image of the actual organism. C. albicans is the most common fungal pathogen to infect humans. Photo courtesy of P. John Hart, Ph.D. clear graphic

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Contact: Will Sansom, 210-567-2579

SAN ANTONIO (April 16, 2014) — A team that includes scientists from the School of Medicine at The University of Texas Health Science Center at San Antonio, Johns Hopkins University and St. Mary's University revealed the structure of a protein that helps a common fungus to infect the body.

The fungal pathogen, Candida albicans, causes yeast infections, diaper rashes and oral thrush. It is the most common fungal pathogen to infect humans. It can also cause a life-threatening blood infection called disseminated candidiasis.

Understanding the fungus’ defense system
"In this study, we determined the three-dimensional structure of a never-before-seen cell wall protein called SOD5 that the organism uses as a defense against the human immune system," said P. John Hart, Ph.D., the Ewing Halsell President's Council Distinguished Chair in biochemistry at the UT Health Science Center and research scientist in the South Texas Veterans Health Care System.

P. John Hart, Ph.D., explained that knowing the structure of the SOD5 protein will help scientists understand its action, which is required for the Candida albicans yeast to survive in its human host. SOD5 represents a new target for the development of antifungal agents.
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P. John Hart, Ph.D., explained that knowing the structure of the SOD5 protein will help scientists understand its action, which is required for the Candida albicans yeast to survive in its human host. SOD5 represents a new target for the development of antifungal agents. clear graphic

 

"SOD5 is a copper-only protein that exhibits significant structural differences from copper/zinc superoxide dismutases (SODs),” Dr. Hart said. “Because SOD5 molecules are widespread throughout fungi, including C. albicans, but are not found in humans, the structural differences can be exploited to develop compounds that specifically target SOD5 to treat a number of widespread fungal infections.”

Current conventional antifungal treatments such as fluconazole can be toxic to the liver in certain individuals, he noted.

Empowering free radicals
“SOD5 is an unprecedented, very powerful antioxidant protein that enables C. albicans to ward off free radicals of the host immune response,” said study senior author Valeria Culotta, Ph.D., professor of biochemistry and molecular biology and environmental health sciences at the Johns Hopkins University Bloomberg School of Public Health. Free radicals are highly reactive molecules that can cause oxidative damage.

The finding was published April 7 online ahead of print by the journal Proceedings of the National Academy of Sciences of the United States of America.

Study collaborators include:
  • Drs. Hart and Culotta;

  • Julie Gleason, Ph.D., and Ryan Peterson, Ph.D., from the Bloomberg School of Public Health at Johns Hopkins University;

  • Ahmad Galaleldeen, Ph.D., and Jessica Waninger-Saroni, B.S., from the Department of Biological Sciences at St. Mary's University in San Antonio;

  • Alexander Taylor, Ph.D., and Stephen Holloway, Ph.D., from the Department of Biochemistry at the UT Health Science Center at San Antonio;

  • Brendan Cormack, Ph.D., from the Department of Molecular Biology and Genetics at the Johns Hopkins University School of Medicine; and

  • Diane Cabelli, Ph.D., from the Department of Chemistry at Brookhaven National Laboratories in Upton, N.Y.
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The University of Texas Health Science Center at San Antonio, one of the country’s leading health sciences universities, ranks in the top 3 percent of all institutions worldwide receiving National Institutes of Health funding. The university’s schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced more than 29,000 graduates. The $765.2 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways “We make lives better®,” visit www.uthscsa.edu.

 
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