Iron is essential for all life. The level of free iron in humans is less than Aspergillus fumigatus and Mycobacterium tuberculosis need. To satisfy their metabolic needs and enable infection, these microbes secrete molecules called siderophores to obtain iron from the host. The synthesis of siderophores requires special enzymes. Sobrado is studying these enzymes. “Our aim is to understand how the enzymes activate molecular oxygen and attach it to the substrate molecules, lysine or ornithine, in the biosynthesis of siderophores,” he said.
He reported in the July 2010 issue of journal Biochemistry that the enzyme from A. fumigatus contains the cofactor flavin adenine dinucleotide (FAD) that reacts with molecular oxygen and forms a stable intermediate. The NSF grant will fund the research to elucidate the mechanism of action and the structure of the enzymes from A. fumigatus and M. tuberculosis, specifically, how they stabilize the intermediate and what regulates the specificity of the enzyme.
For the educational component of the NSF grant, Sobrado is collaborating with a group at the University of Pavia who are experts on protein crystallography. “Our students will travel to Italy to be trained in how to solve the structure of enzymes,” he said. “The goal is to train global scientists.”
The students will include members of Virginia Tech’s Multicultural Academic Opportunities Program and Post-baccalaureate Research and Education Program, as well as high school students who will present their work at the local science fair.
In June 2009, Sobrado received a Ralph E. Powe Junior Faculty Enhancement Award for his research on M. tuberculosis and A. fumigatus and subsequently earned the J. Shelton Horsley Research Award, the highest honor bestowed by the Virginia Academy of Science for original research. His Ph.D. is from Texas A&M University.
The first author on the paper in Biochemistry, Wyatt Chocklett of Mauldin, S.C., was named the outstanding master’s student in the College of Agriculture and Life Sciences at Virginia Tech. He graduated in December 2009 with a master’s degree in biochemistry. The paper by Chocklett and Sobrado, “Aspergillus fumigatus SidA is a highly specific ornithine hydroxylase with bound flavin cofactor,” is available online.
The Fralin Life Science Institute is a member of the Research Institutes of Virginia Tech. Sobrado is affiliated with Fralin’s infectious diseases research area. The Research Institutes of Virginia Tech enhance the university’s ability to address large scale research opportunities by crossing traditional disciplinary and college lines. The six institutes provide clients access to world class expertise across many disciplines and to the scientific and technical capability of specially equipped, advanced laboratories.