Through this award, the Chemistry of Life Processes Program is funding Professor Eunsuk Kim from Brown University to elucidate chemical patterns and principles related to the interaction of NO with [Fe-S] proteins, and the subsequent formation and reactivity of dinitrosyl iron complexes (DNICs)resulting from this interaction. Although NO signaling mechanisms are largely unknown, it has been found that iron-sulfur proteins are one of the main reaction targets for NO, wherein [Fe-S] clusters become modified and convert to DNICs. In this study, the following specific questions will be probed: What are the intrinsic properties and reactivity of DNICs? What are the physiological and/or deleterious roles of DNICs? What happens to the bridging sulfides when [Fe-S] clusters are degraded by NO? How do cells cope with unwanted [Fe-S] modifications by NO? These questions will be addressed by employing synthetic chemistry expertise in combination with a number of spectroscopic, biochemical, bioanalytical and mechanistic studies.
Nitric oxide (NO) is a double-edged sword in biology. While NO is a ubiquitous signaling molecule, misregulation of NO is implicated in numerous conditions including vascular diseases, cancer, and neurodegeneration. The proposed studies will elucidate the interconnections among the key cellular redox components such as [Fe-S] clusters, NO, O2, H2S, and thiols, which will provide fresh insights and solutions to current questions in the field and may lead to new paradigms in the study of biological NO signaling. This project will also be integrated into educational and outreach activities, which will initiate (i) a program dedicated to develop inquiry-based laboratory curricula for high school chemistry and (ii) a student-led problem solving session at a major research conference to promote a culture of active participation from students and underrepresented groups in science.
