Biology subjects

Bhattacharyya, M.

Publications and source records attributed to Bhattacharyya, M..

24 records · Page 2Linked to original sources

bioRxiv2020

Breakage of the Oligomeric CaMKII Hub by the Regulatory Segment of the Kinase

Ca2+/calmodulin dependent protein kinase II (CaMKII) is a dodecameric or tetradecameric enzyme with crucial roles in neuronal signaling and cardiac function. Activation of CaMKII is reported to trigger the exchange of subunits between holoenzymes, which can increase spread of the active state. Using mass spectrometry, we now show that peptides derived from the sequence of the CaMKII- regulatory segment can bind to the CaMKII- hub assembly and break it into smaller oligomers. Molecular dynamics simulations show that the regulatory segments can dock spontaneously at the interface between hub subunits, trapping large fluctuations in hub structure. Single-molecule fluorescence intensity analysis of human CaMKII- isolated from mammalian cells shows that activation of CaMKII- results in the destabilization of the holoenzyme. Our results show how the release of the regulatory segment by activation and phosphorylation could allow it to destabilize the hub, producing smaller CaMKII assemblies that can reassemble to form new holoenzymes.

bioinformatics↗

bioRxiv2020

Origin and Evolution of DNA methyltransferases (DNMT) along the tree of life: A multi-genome survey.

BackgroundCytosine methylation is a common DNA modification found in most eukaryotic organisms including plants, animals, and fungi. (Cytosine-5)-DNA methyltransferases (C5-DNA MTases) belong to the DNMT family of enzymes that catalyze the transfer of a methyl group from S-adenosyl methionine (SAM) to cytosine residues of DNA. In mammals, four members of the DNMT family have been reported: DNMT1, DNMT3a, DNMT3b and DNMT3L, but only DNMT1, DNMT3a and DNMT3b possess methyltransferase activity. There have been many reports about the methylation landscape in different organisms yet there is no systematic report of how the enzyme DNA (C5) methyltransferases have evolved in different organisms. ResultDNA methyltransferases are found to be present in all three domains of life. However, significant variability has been observed in length, copy number and sequence identity when compared across kingdoms. Sequence conservation is greatly increased in invertebrates and vertebrates compared to other groups. Similarly, sequence length has been found to be increased while domain lengths remain more or less conserved. Vertebrates are also found to be associated with more conserved DNMT domains. Finally, comparison between single nucleotide polymorphisms (SNPs) prevailing in human populations and evolutionary changes in DNMT vertebrate alignment revealed that most of the SNPs were conserved in vertebrates. ConclusionThe sequences (including the catalytic domain and motifs) and structure of the DNMT enzymes have been evolved greatly from bacteria to vertebrates with a steady increase in complexity and specificity. This study provides a systematic report of the evolution of DNA methyltransferase enzyme across different lineages of tree of life.

evolutionary biology↗

bioRxiv2019

Flexible linkers in CaMKII control the balance between activating and inhibitory autophosphorylation

The activity of Ca2+/calmodulin-dependent protein kinase II (CaMKII) depends on the balance between activating and inhibitory autophosphorylation (Thr 286 and Thr 305/306, respectively, in the human isoform). Variation in the lengths of the flexible linkers that connect the kinase domains of CaMKII to a central oligomeric hub could alter transphosphorylation rates within a holoenzyme, thereby affecting the balance of autophosphorylation outcomes. Using a single-molecule assay for visualization of CaMKII phosphorylation on glass, we show that the balance of autophosphorylation is flipped between CaMKII- and CaMKII-{beta}, the two principal isoforms in the brain. CaMKII-, with a [~]30 residue kinase-hub linker, readily acquires activating autophosphorylation, which we show is resistant to removal by phosphatases. CaMKII-{beta}, with a [~]200 residue kinase-hub linker, is biased towards inhibitory autophosphorylation. Thus, the responsiveness of CaMKII to calcium signals can be tuned by varying the relative levels of the and {beta} isoforms.

biophysics↗

bioRxiv2019

Global Genetic Cartography of Urban Metagenomes andAnti-Microbial Resistance

We have created a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities across 3 years. This is the first systematic, worldwide study cataloging the urban microbial ecosystem. We identify taxonomically-defined microorganisms collected across three years. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics AMR markers, and novel genetic elements, including 10,928 viral, 1302 bacteria, and 2 archaea novel species. We identify 4,424 species of urban microorganisms and a consistent "core" of 31 species found in nearly all samples that is largely distinct from any human commensal microbiome. Profiles of AMR genes show geographic variation in type and density. Together, these results constitute a high-resolution, global metagenomic atlas, which enables the discovery of new genetic components, highlights potential forensic applications, and provides an essential first draft of the global AMR burden of the worlds cities.

microbiology↗

bioRxiv2018

Chelation therapy using static magnetic field

Static magnetic field (SMF) is reported to mimic chelation agents. In thalassemia blood, SMF minimizes iron overloading effect. In such cells ROS level is reduced, in presence of moderate strength (70mT). Pilot study on transfusion dependent thalassemia, thalassemia carriers and normal red blood clearly indicate the differential effects of SMF on thalassemia, thalassemia carrier and normal cells. SMF also reduces ROS induced DNA damage in lymphocytes. A comparative study on the iron chelating drug deferasirox and SMF treated lymphocytes further confirm our main thesis. This non-invasive therapeutic regime for hemochromatosis may serve the dual purpose of treating, iron overloading and minimizing, cellular damage by lowering the ROS level.

epidemiology↗

bioRxiv2016

Metagenomic Characteristics of Bacterial Response to Petroleum Hydrocarbon Contamination in Diverse Environments as Revealed by Functional Taxonomic Strategies

Microbial remediation of oil polluted habitats remains one of the foremost methods for restoration of petroleum hydrocarbon contaminated environments. The development of effective bioremediation strategies however, require an extensive understanding of the resident microbiome of these habitats. Recent developments such as high-throughput sequencing has greatly facilitated the advancement of microbial ecological studies in oil polluted habitats. However, effective interpretation of biological characteristics from these large datasets remains a considerable challenge. In this study, we have implemented recently developed bioinformatic tools for analyzing 65 publicly available 16S rRNA datasets from 12 diverse hydrocarbon polluted habitats to decipher metagenomic characteristics of bacterial communities of the same. We have comprehensively described phylogenetic and functional compositions of these habitats and additionally inferred a multitude of metagenomic features including 255 taxa and 414 functional modules which can be used as biomarkers for effective distinction between the 12 oil polluted sites. We have identified essential metabolic signatures and also showed that significantly over-represented taxa often contribute to either or both, hydrocarbon degradation and additional important functions. Our findings reveal significant differences between hydrocarbon contaminated sites and establishes the importance of endemic factors in addition to petroleum hydrocarbons as driving factors for sculpting hydrocarbon contaminated bacteriomes.

microbiology↗