- Biochemical and Molecular Research
- Alzheimer's disease research and treatments
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Prion Diseases and Protein Misfolding
- Acute Lymphoblastic Leukemia research
- Heat shock proteins research
- Connexins and lens biology
- Trace Elements in Health
- SARS-CoV-2 and COVID-19 Research
- Enzyme Production and Characterization
- Tuberculosis Research and Epidemiology
- Glycosylation and Glycoproteins Research
- HIV Research and Treatment
- Neurological diseases and metabolism
- Chemical Synthesis and Analysis
- X-ray Diffraction in Crystallography
- Bacterial Genetics and Biotechnology
- Research on Leishmaniasis Studies
- Bacteriophages and microbial interactions
- RNA Interference and Gene Delivery
- Biochemical effects in animals
- Supramolecular Self-Assembly in Materials
- Endoplasmic Reticulum Stress and Disease
- Viral gastroenteritis research and epidemiology
Indian Institute of Technology Delhi
2016-2025
Bangladesh Jute Research Institute
2021-2023
Case Western Reserve University
2003-2013
Indian Institute of Technology Indore
2007
Institute of Microbial Technology
1999-2004
Central Drug Research Institute
2002
University of Tennessee at Knoxville
1987
College of Staten Island
1987
City University of New York
1987
The University of Adelaide
1986
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Thermophilic l-asparaginases display high stability and activity at elevated temperatures. However, they are of limited use in leukemia therapy because their low substrate affinity reduced under physiological conditions. In an attempt to combine with conditions, 3 active-site mutants Pyrococcus furiosus l-asparaginase (PfA) were developed. The mutants, specifically K274E, showed improved enzymatic properties conditions as compared the wild type. All variants thermodynamically stable...
Cardiac hypertrophy and associated heart fibrosis remain a major cause of death worldwide. Phytochemicals have gained attention as alternative therapeutics for managing cardiovascular diseases. These include the extract from plant Terminalia arjuna, which is popular cardioprotectant may prevent or slow progression pathological to failure. Here, we investigated mode action principal bioactive T. arjuna compound, arjunolic acid (AA), in ameliorating hemodynamic load-induced cardiac identified...
Abstract Background Visceral Leishmaniasis (VL) is a fatal vector-borne parasitic disorder occurring mainly in tropical and subtropical regions. VL falls under the category of neglected diseases with growing drug resistance lacking licensed vaccine. Conventional vaccine synthesis techniques are often very laborious challenging. With advancement bioinformatics its application immunology, it now more convenient to design multi-epitope vaccines comprising predicted immuno-dominant epitopes...
Spike (S) protein opening in SARS-CoV-2 controls the accessibility of its receptor binding domains (RBDs) to host receptors and immune recognition. Along evolution variants concern (VOC)─alpha, beta, gamma, delta, omicron─their S proteins showed a higher propensity attain open states. Deciphering how mutations can shape conformational dynamics will contribute understanding viral tropism. Here using microsecond-scale multiple molecular simulations (MDS), we provide insights into kinetic...
One of the most intriguing disease-related mutations in human prion protein (PrP) is Tyr to Stop codon substitution at position 145. This mutation results a Gerstmann–Straussler–Scheinker-like disease with extensive PrP amyloid deposits brain. Here, we provide evidence for spontaneous conversion recombinant polypeptide corresponding Y145Stop variant (huPrP23–144) from monomeric unordered state fibrillar form. characterized by concentration-dependent lag phase and has characteristics...
The principal infectious and pathogenic agent in all prion disorders is a β-sheet–rich isoform of the cellular protein (PrP C ) termed PrP-scrapie Sc ). Once initiated, PrP self-replicating toxic to neuronal cells, but underlying mechanisms remain unclear. In this report, we demonstrate that binds iron transforms -like form (*PrP when human neuroblastoma cells are exposed an inorganic source redox iron. *PrP thus generated itself active, it induces transformation additional , simulating...
Abstract The COVID-19 pandemic has spread across the globe at an alarming rate. However, unlike any of previous global outbreaks availability a large number SARS-CoV-2 sequences provides us with unique opportunity to understand viral evolution in real time. We analysed 1448 full-length (>29000 nt) available and identified 40 single-nucleotide substitutions occurring >1% genomes. Majority were C T or G A. identify C/Gs upstream TTT trinucleotide motif as hotspots for mutations genome....
Prion diseases, or transmissible spongiform encephalopathies (TSEs), are associated with the conformational conversion of cellular prion protein, PrPC, into a protease-resistant form, PrPSc. Here, we show that mutation-induced thermodynamic stabilization folded, α-helical domain PrPC has dramatic inhibitory effect on protein in vitro, as well propagation TSE disease vivo. Transgenic mice expressing human variant increased stability were found to be much more resistant infection agent than...
Small molecule based therapeutic intervention of amyloids has been limited by their low solubility and poor pharmacokinetic characteristics. We report here, the use water soluble poly lactic-co-glycolic acid (PLGA)-encapsulated curcumin emetine nanoparticles (Cm-NPs Em-NPs, respectively), as potential modulators gelsolin amyloidogenesis. Using amyloid-specific dye Thioflavin T (ThT) an indicator along with electron microscopic imaging we show that presence Cm-NPs augmented amyloid formation...
Covalent linkers bridging the domains of multidomain proteins are considered to be crucial for assembly and function. In this report, an exception in which linker a two-domain dimeric L-asparaginase from Pyrococcus furiosus (PfA) was found dispensable is presented. Domains enzyme assembled without into conjoined tetrameric form that exhibited higher activity than parent enzyme. The global shape quaternary structure PfA were also similar wild-type PfA, as observed by their solution scattering...
The pathogenesis of protein misfolding diseases is attributed to the cytotoxicity caused by amyloidogenic prefibrillar aggregates, rather than mature fibrils. presence one or more stretches in different proteins has been proven critical for initiating fibril formation. In present study, we show that two natural compounds, curcumin and emetine, bind tightly (Kd < 1.6 μM) core stretch (182-192) gelsolin (AGel). Binding happens structural orientations, distinctly modulating pathway AGel. While...
Mycobacterium tuberculosis (M. tb), the causative pathogen of (TB) remains leading cause death from single infectious agent. Furthermore, its evolution to multi-drug resistant (MDR) and extremely drug-resistant (XDR) strains necessitate de novo identification drug-targets/candidates or repurpose existing drugs against known targets through drug repurposing. Repurposing has gained traction recently where orphan are exploited for new indications. In current study, we have combined repurposing...
<sc>l</sc>-Asparaginases belong to a family of amidohydrolases that catalyze the conversion of<sc>l</sc>-asparagine into<sc>l</sc>-aspartic acid and ammonia.
Emergence of Amphotericin B (AmB) resistant Leishmania donovani has posed major therapeutic challenge against the parasite. Consequently, combination therapy aimed at multiple molecular targets, based on proteome wise network analysis been recommended. In this regard we had earlier identified and proposed L-asparaginase (LdAI) as a crucial metabolic target. Here report that both LdAI overexpressing axenic amastigote promastigote forms L. survives better when challenged with AmB compared to...