Research

Apurba Kumar Sau

M. Sc.
University of Calcutta

Ph. D.
Tata Institute of Fundamental Research (TIFR), Mumbai

Postdoctoral Research
University of Texas, Austin, USA
Yale University School of Medicine, USA

Email
apurba@nii.res.in

 

Research Interest

Molecular mechanism of regulatory processes, Structural Biochemistry, Antibacterial and antimicrobial target enzymes and their functions, Drug-design, Protein biochemistry

Group Members

Sudeepa Rajan, Nikunj H Raninga,Vineet Sadarangani, Ankita Dutta, Ginto George, Dr. Maskoor Alam, Upma Dave, Sowmiya Gupta and Ramesh Chand

Summary of Research

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 / Fellowships

National Bioscience Award for Career Development (2013)

Selected Publications

  • Arginase of Helicobacter gastric pathogens uses a unique set of non-catalytic residues for catalysis (2017) Ginto George, Mamata Kombrabail, Nikunj Raninga and Apurba Kumar Sau Biophysical Journal,  DOI: 10.1016/j.bpj.2017.02.009
  • Tetrameric Assembly Of hGBP1 Is Crucial For Both Stimulated GMP Formation And Antiviral Activity (2016) Esha Pandita, Sudeepa Rajan, Safikur Rahman, Ranajoy Mullick, Saumitra Das and Apurba Kumar Sau Biochemical Journal, 473, 1745–1757.
  • Structural and Functional Insights into the Regulation of Helicobacter pylori Arginase Activity by an Evolutionary Nonconserved Motif (2013) Abhishek Srivastava, Shiv Kumar Meena, Mashkoor Alam, Shahid M Nayeem, Shashank Deep and Apurba Kumar Sau Biochemistry, 52, 508?
  • Insight into Temperature Dependence of GTPase Activity in Human Guanylate Binding Protein-1 (2012) Anjana Rani, Esha Pandita, Safikur Rahman, Shashank Deep and Apurba Kumar Sau PLoS One 7, e40487.
  • Insight into the Role of a Unique SSEHA Motif in the Activity and Stability of Helicobacter pylori Arginase (2011) Abhishek Srivastava, Nidhi Dwivedi, Uttamkumar Samanta and Apurba Kumar Sau IUBMB Life 63: 1027-1036.
  • Biochemical studies on Helicobacter pylori Arginase: Insight into the Difference in Activity Compared to Other Arginases (2010) Abhishek Srivastava and Apurba Kumar Sau IUBMB Life 62, 906-915.
  • Dimerization And Its Role In GMP Formation By Human Guanylate Binding Proteins (2010) Nazish Abdullah, Meena Balakumari and Apurba Kumar Sau  Biophysical Journal 99: 2235-2244.
  • Role of a Disulphide Bond in Helicobacter pylori arginase (2010) Abhishek Srivastava, Nidhi Dwivedi and Apurba Kumar Sau Biochem. Biophys. Res. Commun 395: 348-351.
  • Role of individual domains and identification of internal GAP in human guanylate binding protein-1(2009) Nazish Abdullah, Bharani Srinivasan, Nir Modiano, Peter Cresswell and  Apurba Kumar Sau J. Mol. Biol 386: 690-703.
  • Effect of fluorinated phosphoenol pyruvate on the mesophillic and thermophillic E. coli 3-deoxy-D-manno-octulosonate-8-phosphate (KDO8P) synthase: A transient kinetic study (2005) Cristina Furdui, Apurba Kumar Sau, Ronald W Woodard, Timor Baasov and Karen S Anderson Biochemistry 44: 7326-35.
  • Probing the role of metal ions in the catalysis of Helicobacter pylori 3-deoxy-D-manno-octulosonate-8-phosphate (KDO8P) synthase using transient kinetic study (2004) Apurba Kumar Sau, Zhili Li and Karen S Anderson J. Biol. Chem 279: 15787-15794.
  • A snapshot of enzyme catalysis using electrospray ionization mass spectrometry (2003) Zhili Li, Apurba K Sau, Shida Shen, Craig Whitehouse, Timor Baasov and Karen S Anderson J. Am. Chem. Soc 125: 9938-9939.
  • Biochemical and kinetic analysis of the RNase active sites of the integrase/tyrosine family site-specific recombinases (2001) Apurba Kumar Sau, Gena D Tribble, Ian Grainge, R F Frohlich, B R Knudsen and Makkuni Jayaram J. Biol. Chem 276: 46612.

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