James Yan, 2009, Chemistry

“Iron is essential to life. All living organisms, including microbes, require iron to live and their ability to acquire iron is extremely important. My internship was focused on researching a mechanism of iron acquisition utilized by bacteria and fungi. Bacteria and fungi can produce molecules called siderophores when they are low on iron. They send the siderophores out into the environment, where they bind to iron. The microbes can then take up the iron-bound siderophores as a source of iron. Siderophores are essential for bacteria living in low iron environments, such as when they are infecting people. The ability to acquire iron is essential for the survival and virulence of the bacteria, and this mechanism is used by such bacteria as the ones that cause pneumonia and tuberculosis.”

“My research studied the mechanism of how one specific siderophore, acinetoferrin, acquired iron from a human iron transport protein, transferrin. Transferrin is the primary iron transport molecule in humans, and could provide a source of iron for infecting bacteria. Discovering the mechanism of siderophore iron acquisition could provide insight in combating bacterial infections and provide a novel way of dealing with antibiotic-resistant strains.”

“Our main approach to studying the siderophore was studying the interaction between transferrin and an analogue of the siderophore. Our hypothesis is that the siderophore displaces a synergistic anion in the protein iron-binding site, then chelates the iron and escapes the binding site by undergoing a conformational change. Our analogue in theory should be able to displace the anion, but lacks the necessary residues to chelate the iron completely. If we can see the analogue complexed with the iron in the protein binding site, then it supports our hypothesis that the first step for iron acquisition is displacement of the anion. We tested this by attempting to iron-load transferrin with the analogue and analyzing the protein with gel electrophoresis and UV-vis spectroscopy. Additionally, we are attempting to use mass spectrometry to find the product of a photochemical reaction of the analogue when it is complexed with iron. Future work also involves studying another analogue.”