A5060237108- Mosquito-borne diseases and control
- SARS-CoV-2 and COVID-19 Research
- Phosphodiesterase function and regulation
- Viral Infections and Outbreaks Research
- Viral Infections and Vectors
- Monoclonal and Polyclonal Antibodies Research
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- vaccines and immunoinformatics approaches
- Protein Kinase Regulation and GTPase Signaling
- RNA and protein synthesis mechanisms
- Immunotherapy and Immune Responses
- Insect symbiosis and bacterial influences
- Heat shock proteins research
- Bacteriophages and microbial interactions
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- COVID-19 Clinical Research Studies
- Computational Drug Discovery Methods
- Cholinesterase and Neurodegenerative Diseases
- Pharmacological Effects of Natural Compounds
- Cancer Immunotherapy and Biomarkers
- Bacterial Genetics and Biotechnology
- Innovative Energy Harvesting Technologies
- Infectious Encephalopathies and Encephalitis
National University of Singapore
2014-2024
Merck (Singapore)
2024
Manipal University Jaipur
2022
University of Hyderabad
2012-2013
The spike (S) protein is the main handle for SARS-CoV-2 to enter host cells via surface angiotensin-converting enzyme 2 (ACE2) receptors. How ACE2 binding activates proteolysis of S unknown. Here, using amide hydrogen–deuterium exchange mass spectrometry and molecular dynamics simulations, we have mapped S:ACE2 interaction interface uncovered long-range allosteric propagation sites necessary host-mediated protein, critical viral entry. Unexpectedly, enhances at a distal S1/S2 cleavage site...
Despite significant progress in cancer immunotherapy recent years, resistance to existing immune checkpoint therapies (ICT) is common. V-domain Ig suppressor of T cell activation (VISTA), a predominantly myeloid regulator, represents promising therapeutic target due its role suppressing proinflammatory antitumor responses myeloid-enriched tumor microenvironments. However, uncertainty around the cognate VISTA ligand has made development effective anti-VISTA antibodies challenging. The...
Severe dengue infections are characterized by endothelial dysfunction shown to be associated with the secreted nonstructural protein 1 (sNS1), making it an attractive vaccine antigen and biotherapeutic target. To uncover biologically relevant structure of sNS1, we obtained infection-derived sNS1 (isNS1) from virus (DENV)-infected Vero cells through immunoaffinity purification instead recombinant (rsNS1) overexpressed in insect or mammalian cell lines. We found that isNS1 appeared as...
Casein kinase 1δ (CK1δ) controls essential biological processes including circadian rhythms and wingless-related integration site (Wnt) signaling, but how its activity is regulated not well understood. CK1δ inhibited by autophosphorylation of intrinsically disordered C-terminal tail. Two CK1 splice variants, δ1 δ2, are known to have very different effects on rhythms. These variants differ only in the last 16 residues tail, referred as extreme C termini (XCT), with marked changes potential...
The changing landscape of SARS-CoV-2 Spike protein is linked to the emergence variants, immune-escape and reduced efficacy existing repertoire anti-viral antibodies. functional activity neutralizing antibodies their quaternary changes occurring as a result antibody-Spike trimer interactions. Here, we reveal conformational dynamics allosteric perturbations binding novel human viral protein. We identified epitope hotspots, associated in that distinguish weak, moderate strong show impact...
Abstract Macrophytes may release allelochemicals that suppress competing phytoplankton, although it is unclear how their effectiveness could be influenced by environmental nutrient conditions. To approach this, we conducted a series of bioassays against the bloom‐forming cyanobacterium Microcystis aeruginosa using extracts and exudates from potentially allelopathic macrophytes under varying We screened six different tropical identified antialgal effects in both Ludwigia adscendens ,...
Abstract HACE1 is an ankyrin repeat (AKR) containing HECT‐type E3 ubiquitin ligase that interacts with and ubiquitinates multiple substrates. While a well‐known tumor suppressor, its structure mode of ubiquitination are not understood. The authors present the cryo‐EM structures human along in vitro functional studies provide insights into how enzymatic activity regulated. comprises N‐terminal AKR domain, middle (MID) C‐terminal HECT domain. Its unique G‐shaped architecture as homodimer,...
Abstract Casein kinase 1 δ (CK1δ) controls essential biological processes including circadian rhythms and Wnt signaling, but how its activity is regulated not well understood. CK1δ inhibited by autophosphorylation of intrinsically disordered C-terminal tail. Two CK1 splice variants, δ1 δ2, are known to have very different effects on rhythms. These variants differ only in the last 16 residues tail, referred as extreme C-termini (XCT), with marked changes potential phosphorylation sites. Here...
ABSTRACT The recent global COVID-19 pandemic has prompted a rapid response in terms of vaccine and drug development targeting the viral pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this work, we modelled complete membrane-embedded SARS-CoV-2 spike (S) protein, primary target therapeutics development, based on available structural data known glycan content. We then used molecular dynamics (MD) simulations to study system presence benzene probes designed enhance...
In cAMP-Protein Kinase A (PKA) signaling, A-kinase anchoring protein scaffolds assemble PKA in close proximity to phosphodiesterases (PDE), kinase-substrates form signaling islands or 'signalosomes'. its basal state, inactive holoenzyme (R2:C2) is activated by binding of cAMP regulatory (R)-subunits leading dissociation active catalytic (C)-subunits. PDEs hydrolyze cAMP-bound the R-subunits generate 5'-AMP for termination and resetting signaling. Mechanistic basis has been derived primarily...
Acrodysostosis represents a group of rare genetic disorders characterized by defective skeletal development and is often accompanied intellectual disabilities. Mutations in the 3'5'cyclic AMP (cAMP)-dependent protein kinase (PKA) type I regulatory subunit isoform α (RIα) phosphodiesterase (PDE) PDE4D have both been implicated impaired PKA regulation acrodysostosis. How mutations on PDEs RIα interfere with cAMP-PKA signaling not understood. can be described two phases. In activation phase,...
Diabetes mellitus is a multifactorial disease and its incidence increasing worldwide. Among the two types of diabetes, type-2 accounts for about 90% all diabetic cases, whereas type-1 or juvenile diabetes less prevalent presents with humoral immune responses against some autoantigens. We attempted to test whether sera patients cross-react mycobacterial heat shock protein 65 (Hsp65) due postulated epitope homologies between Hsp65 an important autoantigen glutamic acid decarboxylase-65...
Abstract Severe dengue infections are characterized by endothelial dysfunction shown to be associated with the secreted nonstructural protein 1 (sNS1), making it an attractive vaccine antigen and biotherapeutic target. To uncover biologically relevant structure of sNS1, we obtained infection-derived sNS1 (isNS1) from DENV-infected Vero cells through immunoffinity purification instead recombinant (rsNS1) overexpressed in insect or mammalian cell lines. We found that isNS1 appeared as...
Orthosteric sites on proteins are formed typically from noncontiguous interacting in three-dimensional space where the composite binding interaction of a biological ligand is mediated by multiple synergistic interactions its constituent functional groups. Through these interactions, ligands stabilize both site and local secondary structure. However, relative energetic contributions individual contacts protein-ligand difficult to resolve. Deconvolution various groups natural inhibitors/ligand...
Abstract The Spike (S) protein is the main handle for SARS-CoV-2 to enter host cells through surface ACE2 receptors. How binding activates proteolysis of S unknown. Here, we have mapped S:ACE2 interface and uncovered long-range allosteric propagation sites critical viral entry. Unexpectedly, enhances dynamics at a distal S1/S2 cleavage site flanking protease docking ~27 Å away while dampening stalk hinge (central helix heptad repeat) regions ~ 130 away. This highlights that are dynamic...
Gram-negative pathogens like Enteropathogenic Escherichia coli (EPEC) utilize the type three secretion system (T3SS) to translocate various effector proteins that are needed "hijack" host for pathogenic survival. Specialized T3SS chaperones inside bacterial cells stabilize these and facilitate their translocation. CesT is a unique multi-cargo chaperone interacts with translocates ~10 different proteins. Here, we report specific interaction between its key effector, NleH2, explore potential...
Aminoglycosides are broad-spectrum antibiotics that bind to the 30S ribosomal subunit (30S) of bacteria and disrupt protein translation. NpmA, a structurally well-characterized methyltransferase identified in an E. coli clinical isolate, catalyzes methylation at A1408 16S rRNA confers aminoglycoside resistance. Using sucrose cushion centrifugation isothermal titration calorimetry, we first confirmed binding between NpmA 30S. Next, performed amide Hydrogen/Deuterium Exchange Mass Spectrometry...
Abstract The pupal cuticle protein from Aedes aegypti (AaPC) inhibits dengue virus (DENV) infection; however, the underlying mechanism of this inhibition remains unknown. Here, we report that AaPC is an intrinsically disordered and interacts with domain I/II DENV envelope via residues Asp59, Asp61, Glu71, Asp73, Ser75, Asp80. can directly bind to cause aggregation DENV, which in turn blocks infection during virus‐cell fusion stage. may also influence viral recognition attachment by...
Severe dengue infections are characterized by endothelial dysfunction shown to be associated with the secreted nonstructural protein 1 (sNS1), making it an attractive vaccine antigen and biotherapeutic target. To uncover biologically relevant structure of sNS1, we obtained infection-derived sNS1 (isNS1) from DENV-infected Vero cells through immunoffinity purification instead recombinant (rsNS1) overexpressed in insect or mammalian cell lines. We found that isNS1 appeared as approximately 250...