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Ruma Banerjee

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Primary Appointment: Biological Chemistry Dept
PubMed Name: Ruma Banerjee
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  Sulfur metabolism furnishes cells with four important reagents: S-adenosylmethionine, which serves as the dominant cellular methyl donor, glutathione, the cell’s most abundant antioxidant, taurine an osmoregulator present at high concentrations and hydrogen sulfide, a gaseous signaling molecule. Our laboratory is interested in deciphering the traffic lights that govern flux of sulfur via competing metabolic pathways at the organismal, cellular, molecular and computational levels to elucidate key regulatory switch points and to illuminate the mechanisms of regulation of individual enzymes. In addition, we are interested in elucidating the mechanism by which cells in the nervous and immune systems, which show a high level of metabolic interdependence on each other, meet their sulfur metabolic needs and identify the sulfur metabolites they use for communication and remodeling of the extracellular redox milieu. We have demonstrated the roles of oxidative stress, sumoylation, androgens and cell-cell communication in regulating key enzymes in the sulfur pathway and elucidated the relative contributions of the transsulfuration enzymes to H2S biogenesis. These basic mechanistic studies are combined with efforts to understand the biochemical penalties incurred by pathogenic mutations leading to rare inborn errors in enzymes in this pathway.
The enzymes in the sulfur metabolic pathway are richly dependent on multiple B vitamins for their catalytic functions. Coincidentally, the two B12 enzymes used by humans reside in the sulfur metabolic neighborhood and are methionine synthase and methylmalonyl-CoA mutase. Despite the paucity of B12-dependent enzymes in humans, the pathway for B12 assimilation and trafficking is rather complex with at least half a dozen proteins being involved. In recent years, the identities of most of these genes have been discovered and our laboratory is elucidating the functions of the individual proteins and the thermodynamics and kinetics of protein-protein interactions in the pathway. Our studies are demonstrating that many of these proteins are chaperones that bind and deliver B12, which is both rare and reactive, while others function both as enzymes, tailoring the active form of the cofactor, and as escorts, delivering B12 to target enzymes. We are studying the reaction mechanisms of the radical B12 enzymes methylmalonyl-CoA mutase and isobutyryl-CoA mutase and are interested in how biology exploits the reactivity of radicals on the one hand while containing it on the other to turn over substrates to products with high fidelity. We use a variety of biophysical (EPR spectroscopy, stopped-flow kinetics) approaches to elucidate the mechanisms and regulation of these clinically important enzymes.