Areas of Interest
Research Foci: Chemical biology of mammalian sulfur metabolism, structural enzymology of human B12 trafficking proteins and enzymes involved in H2S biogenesis and catabolism, redox signaling in immune and neuroimmune function.
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. We are investigating the reaction mechanisms of the human cytosolic enzymes that generate H2S and the mitochondrial enzymes involved in the pathway for H2S oxidation.
The enzymes in the sulfur metabolic pathway are richly dependent on multiple B vitamins for their catalytic functions including vitamin B12. 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 novel enzymatic 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.
Our laboratory is interested also 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.
Honors & Awards
2000 Established Investigator Award, American Heart Association
2001 Pfizer Award (American Chemical Society)
Cracan, V. and Banerjee, R. (2012) A novel coenzyme B12-dependent interconversion of isovaleryl-CoA and pivalyl-CoA. J Biol Chem. 287(6):3723-32.
Vitvitsky, V., Kabil, O., and Banerjee, R. (2012) High Turnover Rates for Hydrogen Sulfide Allow for Rapid Regulation of its Tissue Concentrations, Antiox Redox Signal. 17(1):22-31
Qian, Y., Karpus, J., Kabil, O., Zhu, H-L, Banerjee, R., Zhao, J. and He, C. (2011) A selective fluorescent probe for live cell-monitoring of aqueous sulfide, Nature Commun, a2, 495. 21988911
Koutmos, M., Kabil, O., Smith, J and Banerjee, R. (2010) Structural Basis for Substrate Activation and Regulation by CBS Domains in cystathionine β-synthase. Proc. Natl. Acad. Sci
Kim, J., Gherasim, C. and Banerjee, R. (2008) Decyanation of vitamin B12 by a trafficking chaperone, Proc. Natl. Acad. Sci, 105:14551-14554134
Padovani, D., Labunska, T., Palfey, B.A., Ballou, D. P. and Banerjee, R.(2008) Adenosyltransferase Tailors and Delivers Coenzyme B12. Nature Chem. Biol., 4(3):194-6
Read news and view article at Bandarian V. Delivery of tailor-made cobalamin to methylmalonyl-CoA mutase. Nat Chem Biol. 2008 Mar;4(3):158-9.
Banerjee, R. (2012) Redox Outside the Box: Linking Extracellular Redox Remodeling with Intracellular Redox Metabolism, J. Biol. Chem. 287(7):4397-402.
Kabil, O. and Banerjee, R. (2010) Redox Biochemistry of H2S. J. Biol. Chem. 285: 21903-21907
Banerjee, R., Gherasim, C. and Padovani, D. (2009) The tinker, tailor and mailman in B12 trafficking, Curr. Op. Chem. Biol., 13(4):477-84