Areas of Interest
Research Foci: Chemical biology of hydrogen sulfide signaling, regulation of mammalian sulfur metabolism in health and disease, structural enzymology of human B12 trafficking proteins.
Toxic at high concentrations, H2S is a signaling molecule produced by cells and modulates important physiological processes including blood pressure regulation, inflammation and neuormodulation. Our laboratory is investigating the reaction mechanisms and regulation of enzymes involved in H2S biogenesis and its clearance via oxidation. In addition to the canonical mitochondrial sulfide oxidation pathway, we have recently discovered a new pathway for clearing H2S, which involves hemeproteins. We use a combination of spectroscopic (EPR, fluorescence), kinetic (stopped-flow spectroscopy) and cellular approaches to understand the mechanisms of catalysis and regulation of key enzymes involved in H2S homeostasis. The enzymes involved in sulfur metabolism are richly dependent on multiple B vitamins for their catalytic functions including vitamin B6, folic acid and B12. My laboratory is also studying the intricate network of chaperones that shepherd and tailor vitamin B12 from its point of entry into cells to its target enzymes and whose dysfunction lead to disease. We have been elucidating novel enzymatic functions of the individual proteins and the thermodynamics and kinetics of protein-protein interactions in the pathway that guide B12 delivery without dilution into the cellular milieu. Using a combination of structural, spectroscopic and kinetic approaches we are studying allosteric regulation in the trafficking pathway for cofactor delivery with high fidelity.
Honors & Awards
Li, Z., Lesniak, N. A. and Banerjee, R. (2014) Unusual aerobic stabilization of cob(I)alamin by a B12-trafficking protein allows chemoenzymatic synthesis of organocobalamins. J Am Chem Soc, communication, Nov 10. [Epub ahead of print]
Lofgren, M., Padovani, D., Koutmos, M and Banerjee, R (2013) A Switch III Motif Relays Signaling between a B12 Enzyme and its G-protein Chaperone, Nat Chem. Biol. 9(9):535-9.
Yadav, P.K., Yamada, K., Chiku, T., Koutmos, M. and Banerjee, R. (2013) Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase, J Biol Chem. 288(27):20002-13
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, 107(49):20958-63
- The Chemistry and Biochemistry of B12. Ed. R. Banerjee. John Wiley and Sons, N.Y. 1999.
- Redox Biochemisry. Ed. R. Banerjee.John Wiley and Sons, N.Y. 2007. See Review: Wood MJ. Refocusing redox biochemistry. Nat Chem Biol. 2008 May;4(5):267.
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