Special Bio-Inorganic Chemistry Seminar

Seminar series
Thu, Jan 16 4:00pm
Young Hall 2033
Speaker Daniel W. Bak
Boston College
Department of Chemistry

Proteins that bind metal cofactors, including iron-sulfur (Fe-S) clusters, are ubiquitous in nature and integral to proper cellular function, from DNA repair and tRNA maturation to cofactor biosynthesis and respiratory metabolism. Current in vitro spectroscopic techniques have provided fundamental insight into diverse aspects of Fe-S cluster ligation, including oxidation state and ligand field, but as these metal-protein interactions are non-covalent and often transient and unstable, it is essential to develop novel platforms by which Fe-S clusters can be studied within a native cellular context. By taking advantage of the cysteine ligation sphere of Fe-S clusters, we have developed a chemoproteomic platform that employs cysteine reactivity as a proxy for metal binding. The coupling of cysteine-reactive chemical probes, such as iodoacetamide-alkyne (IA-alkyne), with quantitative mass spectrometry (MS), allows for the global interrogation of the bacterial Fe-S proteome under conditions of both iron-depletion and reduced Fe-S biosynthesis capacity and can achieve global quantification of Fe-S ligation within a native organism. This work provides systems level insight into the steps of iron-sulfur maturation in E. coli, and has resulted in the identification of novel Fe-S proteins involved in diverse biological processes, including tRNA modification, heme transport, and oxidative respiration. As the first method to directly assess global site-specific protein-metal ligation in an endogenous system, this platform will be a powerful tool in the field of bioinorganic chemistry to study and assign in vivo metal ligation.