NSF Award
0956358
This award in the Chemistry of Life Processes program of the Chemistry Division is co-funded by the Biomolecular Systems Cluster in the Division of Molecular and Cellular Biosciences. The award supports work by Professor Syun-Ru Yeh at the Albert Einstein College of Medicine to carry out comparative studies of five novel hemoglobins from three microorganisms, Mycobacterium tuberculosis, Campylobacter jejuni and Escherichia coli. Although hemoglobins are commonly perceived as oxygen carriers, the target globins have been implicated in defense mechanisms against nitric oxide, a key bactericidal agent of the innate host immune system, by utilizing molecular oxygen. The objective of this project is to determine the functional properties of these intriguing oxygen-utilizing globins and to define the mechanism by which these properties are dictated by the protein matrix housing the prosthetic heme group in each globin. To achieve the goal, a complementary set of spectroscopic and rapid-kinetic techniques, combined with biochemical and computational methodologies will be developed and employed in an iterative fashion. The successful completion of this project will better define the physiological roles and functional mechanisms of the bacterial globins that is lacking in the field, thereby advancing fundamental knowledge in the structure-function relationships of heme-proteins. The knowledge thus derived will offer valuable guidelines for the design of efficient blood substitutes carrying molecular oxygen or competent artificial enzymes performing oxygen chemistry for pharmaceutical applications. The multifaceted approach is expected to provide unique training opportunities for graduate, undergraduate and high school students, thereby enhancing the PI's continuing efforts in recruiting, educating and mentoring young scientists, especially women and under-represented minorities.
