I am a senior research scientist with strong skills in applying protein purification, x-ray crystallography and other biophysical techniques to elucidating protein structure. I have successfully used these skills to understand protein conformational changes, protein: ligand interactions and to drive structure-based drug design. I have ten years of industrial research experience in protein purification for biochemical and structural studies.
Primary Affiliation: Stony Brook University, NY - Stony Brook, New York , United States
Tumor immune escape mechanisms have been established as suitable targets for cancer therapy. Among these, tryptophan catabolism plays a central role in creating an immunosuppressive environment, leading to tolerance to potentially immunogenic tumor antigens. Tryptophan catabolism is initiated by either indoleamine 2,3-dioxygenase (IDO1/2) or tryptophan 2,3-dioxygenase 2 (TDO2), resulting in biostatic tryptophan starvation and l-kynurenine production. Recent literature has shown that IDO1 and TDO2 are expressed in multiple tumors, including solid tumors and play key roles in tumor progression other than immune escape. It has also been shown that IDO1 and TDO2 play distinct roles in driving the downstream effectors suggesting that their roles are perhaps non-redundant. Therefore, we developed series of novel small molecule modulators against IDO1 and TDO2 to understand their role in disease biology for multiple indications including cancer, depression and autoimmune disorders.
Biochemical and Biophysical Research Communications
Nicotinamide N-methyltransferase (NNMT) is a S-adenosyl-L-methionine (SAM)-dependent enzyme that catalyzes N-methylation of nicotinamide (NA) and other pyridines to form N-methyl pyridinium ions. Here we report the first ternary complex X-ray crystal structures of monkey NNMT and mouse NNMT in bound form with the primary endogenous product, 1-methyl nicotinamide (MNA) and demethylated cofactor, S-adenosyl-homocysteine (SAH) determined at 2.30 Å and 1.88 Å respectively. The structural fold of these enzymes is identical to human NNMT. It is known that the primary endogenous product catalyzed by NNMT, MNA is a specific inhibitor of NNMT. Our data clearly indicates that the MNA binds to the active site and it would be trapped in the active site due to the formation of the bridge between the pole (long helix, α3) and long C-terminal loop. This might explain the mechanism of MNA acting as a feedback inhibitor of NNMT.
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