A5004432549- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- DNA and Nucleic Acid Chemistry
- RNA Research and Splicing
- RNA modifications and cancer
- Protein Structure and Dynamics
- Amino Acid Enzymes and Metabolism
- Enzyme Structure and Function
- Genomics and Chromatin Dynamics
- SARS-CoV-2 and COVID-19 Research
- Experimental and Theoretical Physics Studies
- DNA Repair Mechanisms
- Electron Spin Resonance Studies
- Drug Transport and Resistance Mechanisms
- Solar and Space Plasma Dynamics
- Glycosylation and Glycoproteins Research
- Lanthanide and Transition Metal Complexes
- Advanced NMR Techniques and Applications
- Enzyme function and inhibition
- Natural Antidiabetic Agents Studies
- thermodynamics and calorimetric analyses
- Ionosphere and magnetosphere dynamics
- Cancer-related molecular mechanisms research
- Genetic factors in colorectal cancer
- Synthesis and biological activity
Gilead Sciences (United States)
2020-2024
Lovely Professional University
2023
Indian Institute of Science Education and Research Mohali
2016-2022
Emory University
2020
National Institutes of Health
2018-2020
New York University
2018-2020
NYU Langone Health
2018-2020
Panjab University
2006-2020
Chandigarh University
2019
National Institute of Neurological Disorders and Stroke
2018-2019
A wide spectrum of clinical manifestations has become a hallmark the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although immunological underpinnings diverse disease outcomes remain to be defined. We performed detailed characterization B cell responses through high-dimensional flow cytometry reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks extrafollicular activation shared...
Abstract/Introduction A wide clinical spectrum has become a hallmark of the SARS-CoV-2 (COVID-19) pandemic, although its immunologic underpinnings remain to be defined. We have performed deep characterization B cell responses through high-dimensional flow cytometry reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks extrafollicular activation as previously described autoimmune settings. Extrafollicular...
GntR/FadR family featuring an N-terminal winged helix-turn-helix DNA-binding domain and a C-terminal α-helical effector-binding oligomerization constitutes one of the largest families transcriptional regulators. Several regulators govern metabolism sugar acids, carbon sources implicated in bacterial-host interactions. Although effectors are known for few acid regulators, unavailability relevant structures has left their allosteric mechanism unexplored. Here, using DgoR, repressor...
Riboswitches are structural cis -acting genetic regulatory elements in 5′ UTRs of mRNAs, consisting an aptamer domain that regulates the behavior expression platform response to its recognition of, and binding to, specific ligands. While our understanding ligand-bound structure adenine riboswitches is based on crystal data well characterized, dynamics ligand-free limited indirect inferences from physicochemical probing experiments. Here we report results 15-nsec-long explicit-solvent...
Abstract In a conformational selection scenario, manipulating the populations of binding‐competent states should be expected to affect protein binding. We demonstrate how in silico designed point mutations within core ubiquitin, remote from binding interface, change specificity by shifting equilibrium ground‐state ensemble between open and closed substates that have similar population wild‐type protein. Binding affinities determined NMR titration experiments agree with predictions, thereby...
DNA bending is believed to facilitate the initial recognition of mismatched base for repair. The repair efficiencies are dependent on both mismatch type and neighboring nucleotide sequence. We have studied several duplexes containing canonical matches: A:T G:C; various mismatches: A:A, A:C, G:A, G:G, G:T, C:C, C:T, T:T; a bis-abasic site: X:X. Free-energy profiles were generated using umbrella sampling. highest energetic cost associated with observed matches while free energies lower in...
Abstract The BLM helicase protein plays a vital role in DNA replication and the maintenance of genomic integrity. Variation gene resulted defects repair mechanism was reported to be associated with Bloom syndrome (BS) cancer. Despite extensive investigation proteins humans, no attempt has previously been made comprehensively analyse single nucleotide polymorphism (SNPs) gene. In this study, comprehensive analysis SNPs on performed identify, characterize validate pathogenic using...
Aqueous interfaces of liquid crystals (LCs) are widely explored in the design functional to recapitulate key aspects biomolecular interactions cellular milieu. Herein, using aqueous LC dispersions, we explore between mitochondrial cardiolipin and membrane-associated cytochrome c which play a pivotal role apoptotic signaling cascade. Conventional techniques used decipher ordering at droplet interface fail give information about molecular level. Besides, owing complexity systems multiple...
The effect of reduced dielectric environments on the conformational sampling DNA was examined through molecular dynamics simulations. Different were used to model one aspect cellular environments. Implicit solvent based Generalized Born methodology reflect different in simulation results show a tendency structures favor noncanonical A-like conformations rather than canonical A- and B-forms as result suggest that response may be sufficient enhance compared dilute conditions.
Methylenetetrahydrofolate reductase (MTHFR) links the folate cycle to methionine in one-carbon metabolism. The enzyme is known be allosterically inhibited by SAM for decades, but importance of this regulatory control metabolism has never been adequately understood. To shed light on issue, we exchanged selected amino acid residues a highly conserved stretch within region yeast MTHFR create series feedback-insensitive, deregulated mutants. These were exploited investigate impact defective...
The emergence of a new coronavirus (CoV), severe acute respiratory syndrome 2 (SARS-CoV-2), responsible for disease in humans termed 2019 (COVID-19), became global threat health and the economy. SARS-CoV-2 genome is about 29,800-nucleotide-long plus-strand RNA that can form functionally important secondary higher-order structures called cis -acting elements. These elements interact with viral proteins, host or other RNAs be involved regulating translation replication processes encapsidation...
We describe the discovery and preclinical characterization of a potent selective lysophosphatidic acid receptor 1 (LPAR1) antagonist with direct-acting antifibrotic mechanism.
Chronic constipation can lead to fecal impaction. It also rarely catastrophic complications like perforation, colonic obstruction, and peritonitis. We report a rare case of stercoral sigmoid perforation with peritonitis pneumoperitoneum, which was diagnosed on preoperative CT scan.
Mammalian Quaking (QKI) protein, a member of STAR family proteins is mRNA-binding which post-transcriptionally modulates the target RNA. QKI protein possesses maxi-KH domain composed single heterogeneous nuclear ribonucleoprotein K homology (KH) and C-terminal QUA2 domain, that binds sequence-specific RNA recognition element (QRE), CUAAC. To understand binding specificities for different mRNA sequences KH-QUA2 we introduced point mutations at positions in QRE resulting twelve with nucleotide...
Several GntR/FadR transcriptional regulators govern sugar acid metabolism in bacteria. Although effectors have been identified for a few regulators, the mode of effector binding is unknown. Even overall FadR subfamily, there are limited details on effector-regulator interactions. Here, we effector-binding cavity Escherichia coli DgoR, subfamily repressor D-galactonate that employs as its effector. Using genetic screen, isolated several dgoR superrepressor alleles. Blind docking suggested...
Abstract In a conformational selection scenario, manipulating the populations of binding‐competent states should be expected to affect protein binding. We demonstrate how in silico designed point mutations within core ubiquitin, remote from binding interface, change specificity by shifting equilibrium ground‐state ensemble between open and closed substates that have similar population wild‐type protein. Binding affinities determined NMR titration experiments agree with predictions, thereby...
Intron diversity facilitates regulated gene expression and alternative splicing. Spliceosomes excise introns after recognizing their splicing signals: the 5'-splice site (5'ss), branchpoint (BP) 3'-splice (3'ss). The latter two signals are recognized by U2 small nuclear ribonucleoprotein (snRNP) its accessory factors (U2AFs), but longer spacings between them result in weaker Here, we show that excision of with a BP-distant 3'ss (e.g. rap1 intron 2) requires ubiquitin-fold-activated regulator...
STAR proteins are evolutionary conserved mRNA-binding that post-transcriptionally regulate gene expression at all stages of RNA metabolism. These possess domain recognizes identical regulatory elements as YUAAY. Recently reported crystal structures show is composed N-terminal QUA1, K-homology (KH) and C-terminal QUA2, mRNA binding mediated by KH-QUA2 domain. Here, we present simulation studies done to investigate protein, mammalian Quaking protein (QKI). We carried out conventional MD...
Allostery is conformation regulation by propagating a signal from one site to another distal site. This study focuses on the long-range communication in DNA mismatch repair proteins MutS and its homologs where intramolecular signaling has travel over 70 Å couple lesion detection ATPase activity eventual downstream repair. Using dynamic network analysis based extensive molecular dynamics simulations, multiple preserved pathways were identified that would allow such signaling. The appear...