Biology subjects

Bhat, D. S.

Publications and source records attributed to Bhat, D. S..

3 recordsLinked to original sources

bioRxiv2026

Pathway-Based Analysis of Essential Metabolic Enzymes as Drug Targets

Tuberculosis (TB) , caused by Mycobacterium tuberculosis , remains a major global health crisis, aggravated by rapid emergence of multidrug-resistant (MDR) and extensively drug resistant (XDR) strains. Conventional drug discovery is time-consuming and expensive, making computational target identification and drug repurposing as crucial strategies to accelerate the development of novel antitubercular therapies. This study aimed to identify and prioritize the metabolic enzymes as potential drug targets through pathway based analysis and to screen the FDA-approved drug library for potential canidates for drug repurposing. Based on the pathway analysis, para-aminobenzoate synthase component I (PabB) was selected as a potential drug target owing to its role in folate biosynthesis. Subesquently, an FDA-approved drug library was screened based on ADMET properties and selected compounds were used for molecular docking agaist the protein. Molecular docking through DiffDock and validation using GNINA revealed that Ligand 5 and Ligand 27 exhibit favourable interaction profiles within the binding region of PabB, and emerged as potential candidates for further investigation in drug repurposing. The identification of PabB protein asan essential metabolic drug target, coupled with screening of FDA-approved drugs as inhibitors, provides a promising framework for anti tubercular drug discovery.

bioinformatics↗

bioRxiv2023

Human hnRNPA1 reorganizes telomere-bound Replication Protein A

Human replication protein A (RPA) is a heterotrimeric ssDNA binding protein responsible for many aspects of cellular DNA metabolism. Dynamic interactions of the four RPA DNA binding domains (DBDs) with DNA control replacement of RPA by downstream proteins in various cellular metabolic pathways. RPA plays several important functions at telomeres where it binds to and melts telomeric G-quadruplexes, non-canonical DNA structures formed at the G-rich telomeric ssDNA overhangs. Here, we combine single-molecule total internal reflection fluorescence microscopy (smTIRFM) and mass photometry (MP) with biophysical and biochemical analyses to demonstrate that heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) specifically remodels RPA bound to telomeric ssDNA by dampening the RPA configurational dynamics and forming a ternary complex. Uniquely, among hnRNPA1 target RNAs, telomeric repeat-containing RNA (TERRA) is selectively capable of releasing hnRNPA1 from the RPA-telomeric DNA complex. We speculate that this telomere specific RPA-DNA-hnRNPA1 complex is an important structure in telomere protection. One Sentence SummaryAt the single-stranded ends of human telomeres, the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) binds to and modulates conformational dynamics of the ssDNA binding protein RPA forming a ternary complex which is controlled by telomeric repeat-containing RNA (TERRA).

biophysics↗

bioRxiv2020

Transient systemic inflammation in adult male mice results in underweight progeny

ProblemWhile the testes represent an immune privileged organ, there is evidence that systemic inflammation is accompanied by local inflammatory responses. We therefore examined if transient systemic inflammation caused any inflammatory and functional consequences in murine testes. Method of StudyUsing a single systemic administration of Toll-like receptor (TLR) agonists [lipopolysaccharide (LPS) or peptidoglycan (PG) or polyinosinic-polycytidylic acid (polyIC)] in young adult male mice, we assessed testicular immune-inflammatory landscape and reproductive functionality. ResultsOur findings demonstrated a significant induction of testicular TNF-, IL-1{beta} and IL-6 transcripts within 24 h of TLR agonist injection. By day 6 these cytokine levels returned to baseline. While there was no change in caudal sperm counts at early time points, eight weeks later, two-fold decrease of sperm count and reduced testicular testosterone levels was evident. When these mice were subjected to mating studies, no differences in mating efficiencies or litter sizes were observed compared to controls. Nonetheless, the neonatal weights of progeny from LPS/PG/polyIC treated sires were significantly lower than controls. Postnatal weight gain up to three weeks was also slower in the progeny of LPS/polyIC treated sires. Placental weights at 17.5 days post-coitum were significantly lower in females mated to LPS and polyIC treated males. Given this likelihood of an epigenetic effect, we found lower testicular levels of histone methyl-transferase enzyme, mixed-lineage leukemia-1, in mice given LPS/PG/polyIC eight weeks earlier. ConclusionExposure to transient systemic inflammation leads to transient local inflammation in the testes, with persistent sperm-mediated consequences for fetal development.

immunology↗