- Food Allergy and Anaphylaxis Research
- Allergic Rhinitis and Sensitization
- Genomics and Chromatin Dynamics
- Contact Dermatitis and Allergies
- Neuroscience and Neuropharmacology Research
- RNA and protein synthesis mechanisms
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Sirtuins and Resveratrol in Medicine
- RNA Interference and Gene Delivery
- Insect and Pesticide Research
- Cellular transport and secretion
- Pluripotent Stem Cells Research
- Natural product bioactivities and synthesis
- Epigenetics and DNA Methylation
- Bacterial Genetics and Biotechnology
- Advanced biosensing and bioanalysis techniques
- Bacterial biofilms and quorum sensing
- Natural Compounds in Disease Treatment
- Amyotrophic Lateral Sclerosis Research
- Biochemical effects in animals
- DNA Repair Mechanisms
- Nuclear Receptors and Signaling
- X-ray Diffraction in Crystallography
- Enzyme Production and Characterization
National Institute of Mental Health and Neurosciences
2019-2024
Nanyang Technological University
2016-2021
SPring-8
2012-2016
Laurus labs (India)
2010
Industrial Credit and Investment Corporation of India
2010
University of Basel
2007-2009
Abstract We report the three-dimensional structure of complex between major respiratory grass pollen allergen Phl p 2 and its specific human IgE-derived Fab. The 2-specific IgE Fab has been isolated from a combinatorial library constructed lymphocytes allergic patient. When variable domains were grafted onto IgG1, resulting Ab (huMab2) inhibited strongly binding patients’ to as well allergen-induced basophil degranulation. Analysis by surface plasmon resonance yielded very low dissociation...
Cyclic di-GMP (c-di-GMP) is a ubiquitous bacterial second messenger that involved in the regulation of cell surface-associated traits and persistence infections. Omnipresent GGDEF EAL domains, which occur various combinations with regulatory catalyze c-di-GMP synthesis degradation, respectively. The crystal structure full-length YkuI from Bacillus subtilis, composed an domain C-terminal PAS-like domain, has been determined its native form complex Ca(2+). exhibits triose-phosphate...
The 'acidic patch' is a highly electronegative cleft on the histone H2A-H2B dimer in nucleosome. It fundamental motif for protein binding and chromatin dynamics, but cellular impact of targeting this potentially therapeutic site with exogenous molecules remains unclear. Here, we characterize family binuclear ruthenium compounds that selectively target nucleosome acidic patch, generating intra-nucleosomal cross-links as well inter-nucleosomal cross-links. In contrast to cisplatin or...
Abstract The poly(ADP-ribose) polymerase, PARP1, plays a key role in maintaining genomic integrity by detecting DNA damage and mediating repair. γH2A.X is the primary histone marker for double-strand breaks PARP1 localizes to H2A.X-enriched chromatin sites, but basis this association not clear. We characterize kinetics of binding variety nucleosomes harbouring breaks, which reveal that associates faster with (γ)H2A.X- versus H2A-nucleosomes, resulting higher affinity former, maximal...
All thermophilic and hyperthermophilic archaea encode homologs of dimeric Alba (Sac10b) proteins that bind cooperatively at high density to DNA. Here, we report the 2.0 Å resolution crystal structure an Alba2 (Ape10b2)-dsDNA complex from Aeropyrum pernix K1. A rectangular tube-like encompassing duplex DNA reveals positively charged residues in monomer-monomer interface each dimer packing on either side bound dsDNA successive minor grooves. The extended hairpin loop connecting strands β3 β4...
Dau c 1 is a major allergen of carrot (Daucus carota) which displays IgE cross-reactivity with the homologous birch-pollen Bet v 1. The crystal structure has been determined to resolution 2.7 Å, revealing tight dimers. similar those allergens from celery, Api g 1, and birch pollen, Electron density observed in hydrophobic cavity each monomer modelled polyethylene glycol oligomers varying length. Comparison surface topology physicochemical properties revealed that they may have some, but not...
α-Synuclein (αS) plays a key role in Parkinson's disease (PD). The αS nuclear role, its binding affinity and specificity to histones dsDNA remains unknown. Here, we have measured the ( Kd ) between wild-type (wt) PD-specific S129-phosphorylation mimicking (S129E) mutant with full-length flexible tail truncated individual core (H2a, H2b, H3, H4), linker histone (H1), carried out αS-dsDNA interaction studies. This study revealed that αS(wt) interacts specifically N-terminal tails of H4, H1....
Methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening human infections. Bacteriophage-encoded endolysins degrade the cell walls of Gram-positive bacteria by selectively hydrolyzing peptidoglycan layer and thus are promising candidates to combat bacterial PlyGRCS, S. aureus-specific bacteriophage endolysin, contains a catalytic CHAP domain cell-wall binding SH3_5 connected linker. Here, we show crystal structure full-length PlyGRCS refined 2.1 Å resolution. In addition,...
Astroglia play crucial neuroprotective roles by internalizing pathogenic aggregates and facilitating their degradation. Here, we show that α-SYN protofibril-induced organelle toxicities reactive oxygen species (ROS) cause premature cellular senescence in astrocytes astrocyte-derived cancer cells, resulting a transient increase the biogenesis of tunneling nanotubes (TNTs). TNT-biogenesis TNT-mediated cell-to-cell transfer lead to clearance α-SYN-induced toxicities, reduction ROS levels,...
Structural characterization of chromatin is challenging due to conformational and compositional heterogeneity in vivo dynamic properties that limit achievable resolution vitro. Although the maximum for solving structures large macromolecular assemblies by electron microscopy has recently undergone profound increases, X-ray crystallographic approaches may still offer advantages certain systems. One such system compact chromatin, wherein crystalline state recapitulates crowded molecular...
Abstract Astroglia play crucial neuroprotective roles by internalizing pathogenic aggregates and facilitating its degradation. Here, we show, that α-SYN protofibril-induced organelle toxicities reactive oxygen species (ROS) cause premature cellular senescence in astrocytes origin cancer cells, resulting a transient increase biogenesis of tunneling nanotubes (TNTs). TNT-biogenesis TNT-mediated cell-to-cell transfer lead to clearance α-SYN-induced toxicities, reduction ROS levels, reversal...
ABSTRACT α-Synuclein (αSyn) plays a critical role in the pathogenesis of ‘Synucleinopathies’. Although increased nuclear αSyn localization induces neurotoxicity, its definitive physiological remains elusive. Previous studies on are limited to interactions with individual histones and dsDNA, leaving significant gap understanding assembled histone H2a-H2b dimer (H3-H4) 2 tetramer, as well chromatin regulation. Here, we demonstrated that binds specifically both high affinity. Truncation...
Staphylococcus aureus causes a wide range of infections, from mild skin conditions to severe, life-threatening diseases. Bacteriophage endolysins exhibit selective capacity degrade the peptidoglycan layer Gram-positive bacteria, making promising biotherapeutic agents against antibiotic-resistant infections. PlyGRCS, specific endolysin derived S. aureus, comprises catalytic CHAP domain and cell-wall binding SH3_5 connected by linker. Ca
α-Synuclein (αSyn) aggregation is associated with Parkinson's disease (PD). The region αSyn36-42 acts as the nucleation 'master controller' and αSyn1-12 a 'secondary site'. They drive monomeric αSyn to aggregation. Small molecules targeting these motifs are promising for disease-modifying therapy. Using computational techniques, we screened thirty phytochemicals binding. top three compounds were experimentally validated their binding affinity. Amongst them, celastrol showed high NMR analysis...
Fatty-acid degradation is an oxidative process that involves four enzymatic steps and referred to as the β-oxidation pathway. During this process, long-chain acyl-CoAs are broken down into acetyl-CoA, which enters mitochondrial tricarboxylic acid (TCA) cycle, resulting in production of energy form ATP. Enoyl-CoA hydratase (ECH) catalyzes second step pathway by syn addition water double bond between C2 C3 a 2- trans -enoyl-CoA, formation 3-hydroxyacyl CoA. Here, crystal structure ECH from...