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 neuoromodulation. 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
Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repair.
Ruetz M, Campanello GC, Purchal M, Shen H, McDevitt L, Gouda H, Wakabayashi S, Zhu J, Rubin EJ, Warncke K, Mootha VK, Koutmos M, Banerjee R.
Science 2019; 366: 589-93.
A Catalytic Trisulfide in Human Sulfide Quinone Oxidoreductase Catalyzes Coenzyme A Persulfide Synthesis and Inhibits Butyrate Oxidation.
Landry AP, Moon S, Kim H, Yadav PK, Guha A, Cho US, Banerjee R.
Cell Chem Biol. 2019, in press.
Hydrogen sulfide perturbs mitochondrial bioenergetics and triggers metabolic reprogramming in colon cells.
Libiad M, Vitvitsky V, Bostelaar T, Bak DW, Lee HJ, Sakamoto N, Fearon ER, Lyssiotis CA, Weerapana E, Banerjee R.
J Biol Chem. 2019; 294: 12077-90.
Allosteric Regulation of Oligomerization by a B12 Trafficking G-Protein Is Corrupted in Methylmalonic Aciduria.
Ruetz M, Campanello GC, McDevitt L, Yokom AL, Yadav PK, Watkins D, Rosenblatt DS, Ohi MD, Southworth DR, Banerjee R.
Cell Chem Biol. 2019; 26: 960-9.
S-3-Carboxypropyl-L-cysteine specifically inhibits cystathionine γ-lyase-dependent hydrogen sulfide synthesis.
Yadav PK, Vitvitsky V, Kim H, White A, Cho US, Banerjee R.
J Biol Chem. 2019; 294: 11011-22.
Sacrificial Cobalt-Carbon Bond Homolysis in Coenzyme B12 as a Cofactor Conservation Strategy.
Campanello GC, Ruetz M, Dodge GJ, Gouda H, Gupta A, Twahir UT, Killian MM, Watkins D, Rosenblatt DS, Brunold TC, Warncke K, Smith JL, Banerjee R.
J Am Chem Soc. 2018; 140: 13205-8.
Mechanism-based inhibition of human persulfide dioxygenase by γ-glutamyl-homocysteinyl-glycine.
Kabil O, Motl N, Strack M, Seravalli J, Metzler-Nolte N, Banerjee R.
J Biol Chem. 2018; 293: 12429-39.
The Human Knockout Gene CLYBL Connects Itaconate to Vitamin B12.
Shen H, Campanello GC, Flicker D, Grabarek Z, Hu J, Luo C, Banerjee R, Mootha VK.
Cell. 2017; 171: 771-82.
Chemical Biology of H2S Signaling through Persulfidation.
Filipovic MR, Zivanovic J, Alvarez B, Banerjee R.
Chem Rev. 2018; 118: 1253-1337.
Catalytic promiscuity and heme-dependent redox regulation of H2S synthesis.
Curr Opin Chem Biol. 2017; 37: 115-21.
Navigating the B(12) road: assimilation, delivery, and disorders of cobalamin.
Gherasim C, Lofgren M, Banerjee R.
J Biol Chem. 2013; 288: 13186-93.
For a list of publications from PubMed, click HERE