Dr. Apurba Kumar Sau

The primary focus of our research is to understand how enzymes/receptors work at the molecular level and this helps in-depth mechanistic understanding and thereby provides a more effective way of modulating their functions. We are mainly interested in those enzymes/receptors that are important targets for the design of antibiotics and antimicrobial agents etc. The functional studies along with the structural data may provide to design inhibitors/drug candidates for therapeutic purposes. We are using a combination of molecular biology, biochemical, kinetic, thermodynamic and structural approaches such as rapid transient kinetics, mass spectrometry, circular dichroism, fluorescence, isothermal calorimeter and x-ray crystallography to address these problems.

Interferons induced GTPases
Interferons (IFN) are immunomodulatory cytokines that mediate anti-pathogenic and anti-proliferative effects in cells. The guanylate-binding proteins, known as GTPases are among the most abundant proteins induced by IFN-gamma. They constitute two families of GTP binding proteins with molecular masses 47 and 65-67 kDa, respectively. The p47 GTP binding proteins have been indentified in mammals but the p67 GBPs (hGBP1, hGBP2 etc) have been found in all vertebrates including human, mouse etc. In contrast to all other GTPases, which hydrolyze GTP to GDP, hGBP1 catalyzes the hydrolysis of GTP to a mixture of GMP and GDP, with GMP being the major product. It has been found that this protein blocks the replication of vesicular stomatitis, encephalomyocarditis viruses in HeLa cells and more recently influenza, whereas the mechanism leading to this effect is unknown and it also antagonizes the proliferation and angiogenic activity of endothelial cells on inflammation. However, the antiviral activity is much weaker than human MxA, another group of proteins within the super family of dynamin related large GTPase, which are induced by interferon-alpha. The p47 GTPases act as antimicrobials in cells; they appear to suppress Toxoplasma gondii, Listeria monocytogenes, Mycobacterium spp. The structure-functional relationship is important in view of understanding how these proteins work at the molecular level. We recently identified an alpha helix of the intermediate domain which acts as an internal GAP (GTPase activating protein) in hGBP1 (J. Mol. Biol (2009), 386, 690-703).

Biosynthetic pathways in Helicobacter pylori
Helicobacter pylori, a human pathogen infects the stomach of half of the population worldwide and causes chronic active gastritis, which can lead to peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma. Current antibiotic therapy requires a combination of drugs with long term treatment. Moreover, the emergence of drug-resistant strains in human pathogens has gained further attention towards the development of new drugs. We are therefore interested in the biosynthetic pathways of the microorganism that are not present in mammals and hence may be an attractive target for the design of new antibiotics.

Our lab would be primarily interested in the following topics:

• To understand the mechanism of these enzymes using various approaches
• To investigate the mechanism by which hGBP-1 blocks the replication of VSV and EMCV
• To understand how p47 GTP-binding proteins act as antimicrobial in cells

Awards:
• Fellow of National Academy of Sciences, India (2017)
• National Bioscience Award for Career Development (2013)