Profile
Our research is focused on the mechanistic study of enzyme regulation relating to human and bacterial enzymes. In human enzymes, our interest is to understand the regulation of GTP hydrolysis to GDP or GMP in interferon-gamma-induced large GTPases human guanylate binding proteins (hGBPs) and their role in immunity. We recently demonstrated a novel mechanism for the stimulation of GMP formation in human GTPase, hGBP1, which makes this family functionally distinct from other known GTPases, and thus represents a major contribution to GTPase research. The demonstration, which shows that the proliferation of HCV can be controlled by the hGBP1-mediated stimulated GMP, is an interesting finding with significant physiological ramifications. We are also studying arginine metabolism in Helicobacter pylori, which is crucial for the pathogenesis and survival of the bacterium. We discovered novel noncatalytic aromatic and nonaromatic triads, unique to the arginases of all Helicobacter gastric pathogens, which have huge potential for developing a new class of therapeutic inhibitors. We identified a new inhibitor that disrupts polyamine biosynthesis, which is critical for bacterial survival.
Current Focus Areas
Enzyme regulation and its importance in Biology. Human enzymes for understanding their role in immunity, and bacterial enzymes for designing small molecule inhibitors and developing new therapeutics.
Selected Publications
1. Rashmi D, Gupta S, Kausar T and Sau A K* (2024) Helical domain of hGBP3 cannot stimulate the second phosphate cleavage of GTP. J. Biol. Chem,300:105696-18.
2. Mittal M, Kausar T, Rajan S, Rashmi D and Sau A K* (2023) Difference in Catalytic Loop Repositioning Leads to GMP Variation between Two Human GBP Homologues. Biochemistry, 62, 1509-1526 [Highlighted on the front cover of Biochemistry, volume 62, issue 9].
3. Sarkar D, Vijayan R, Gourinath S and Sau A K* (2022) A unique aromatic cluster near the active site of H. pylori CPA is essential for catalytic function. Biophysical Journal, 121, 248-262.
4. Srivastava A, Meena SK, Alam M, Nayeem S.M, Deep S and Sau A K* (2013) Structural and Functional Insights into the Regulation of Helicobacter pylori Arginase Activity by an Evolutionary Non-conserved Motif. Biochemistry, 52, 508−519.
5. Abdullah N, Srinivasan B, Modiano N, Cresswell P and Sau AK* (2009) Role of individual domains and identification of internal GAP in human guanylate binding protein-1. J. Mol. Biol, 386, 690-703.