Biology subjects

Ulaganathan, V.

Publications and source records attributed to Ulaganathan, V..

2 recordsLinked to original sources

bioRxiv2025

Structural and Boolean Network Modeling of the Levan Biosynthetic Pathway in Bacillus subtilis.

MotivationLevan is a fructose polymer with applications in the creation of hydrogels for drug delivery and wound healing. In industrial biotechnology. Bacillus subtilis is the key organism for producing levan. However, the metabolic models of Bacillus subtilis available do not include the biosynthesis of levan. To understand levan biosynthesis in B. subtilis, we employed structural systems biology integrating known structural details of proteins in the B. subtilis metabolic pathway to create a structure-annotated genome-scale metabolic model (GEM). To fill gaps in structural information about the enzymes, AlphaFold2 was used. Thus, this study enhances the metabolic model of B. subtilis by incorporating the biosynthesis of levan and including structural information about the proteins involved. ResultsThe manually curated model links proteins and reactions to protein data bank (PDB) entries, providing structural perspectives previously overlooked in GEMs. We mapped 508 PDB structures to 168 UniProt IDs to unravel 331 out of 1250 reactions (26.5%) in B. subtilis with focused coverage of sacB, sacC, sacX/Y, levD/E/F/G, and sacP. The structural layer does not alter stoichiometry or constraints unless explicitly parameterized. This structure-annotated resource enables the systematic testing of phenotype predictions and design strategies. Our structure-based metabolic model advances the understanding of levan production and microbial metabolism, facilitating sustainable and efficient biotechnological processes for industrial applications. Availability and implementationData available at the github page (https://github.com/raghuyennamalli/levan_ssbio)

systems biology↗

bioRxiv2025

Calcium Dependent Conformational Changes in Human Transglutaminase 2 and its Implications in Celiac Disease

Transglutaminase 2 (TG2) serves as a modifiable transamidating acyltransferase that precipitates calcium-induced protein alterations. The enzyme plays a crucial role in the cell and disease states, such as tissue repair, calcium signal transduction, celiac disease, and cancer. It is implicated in protein crosslinking and has been found in high concentrations in the small intestines of those with celiac disease. The function of TG2 hinges upon calcium ions binding to particular sites on the enzyme. In this study, we delve into the contribution of calcium-responsive transglutaminase 2 (TG2) in celiac disease, utilizing both molecular dynamics simulations and coarse-grained models, and investigate the impact of non-synonymous single nucleotide polymorphisms (nsSNPs) on TG2. Molecular dynamics reveal prominent conformational differences between the open and closed conformations. In the coarse-grained model, key residues are found adjacent to the active site in the open conformation, while in the closed conformation, key residues are distant from the active site. We further explore the functional impact of non-synonymous single nucleotide polymorphisms (nsSNPs) in TG2 using both sequence-based and structure-based computational tools. Through a consensus approach, we identify ten nsSNPs that are predicted to destabilize TG2 or alter its structural flexibility, with mutations such as R48H, E186Q, C277S, and E549G likely to influence active site accessibility and calcium coordination. The findings from this research enhances our understanding of the molecular processes underpinning celiac disease and helps facilitate innovative treatment approaches that target calcium-responsive TG2.

bioinformatics↗