Biology subjects

Kumar, R. R.

Publications and source records attributed to Kumar, R. R..

3 recordsLinked to original sources

bioRxiv2025

Modulation of Saccharomyces cerevisiae Stm1_N1-113 and human AB42 amyloid fibril morphology by 3,3'-(acridine-4,5-diylbis(methylene))bis(1-(carboxymethyl)-1H-benzimidazolium) dibromide

Acridine derivatives are among the oldest and most effective classes of chemotherapeutic agents, exhibiting a broader spectrum of bioactivities like antitumor, antifungal, antimicrobial, and antiviral. They remain a preferred choice for molecular imaging of amyloid as well as for inhibiting amyloid fibrillation or stabilizing the fibril. This study reports the effect of a newly reported acridine compound 3,3-(acridine-4,5-diylbis(methylene)) bis(1-(carboxymethyl)-benzimidazolium) dibromide (henceforth, Ac-BIM-acid) on the amyloid-like fibrillation of N-terminal region of Saccharomyces cerevisiae Stm1 protein (Stm1_N1-113) and human A{beta}42. Modulation of Stm1_N1-113 amyloid-like structures at 400 {micro}M concentration with respect to varying concentrations of Ac-BIM-acid is revealed by AFM and NMR. While 2D-HSQC NMR spectra show the binding of Ac-BIM-acid with 400 {micro}M Stm1_N1-113, AFM captures the morphological changes of Stm1_N1-113 in response to 1 mM and 2.5 mM Ac-BIM-acid at physiological salt concentration in a time-dependent manner. Similarly, Ac-BIM-acid is shown to modulate the amyloid morphology of human A{beta}42 protein, responsible for Alzheimers disease, captured in AFM. Docking studies carried out indicate that the hydrophobic acridine ring binds at the hydrophobic pocket of the N-terminal {beta}-sheet and its neighboring {beta}-sheet of the A{beta}42 monomorphic fibril. Thus, Ac-BIM-acid would be yet another addition to the class of acridine derivatives that modulate amyloid fibrillation.

molecular biology↗

bioRxiv2021

Knockdown of a novel ATPase domain of capsid protein inhibits genome packaging in potato leaf roll virus

Potato leaf roll virus (PLRV) uses powerful molecular machines to package its genome into a viral capsid employing ATP as fuel. Although, recent bioinformatics and structural studies have revealed detailed mechanism of DNA packaging, little is known about the mechanochemistry of genome packaging in small plant viruses such as PLRV. We have identified a novel P-loop-containing ATPase domain with two Walker A-like motifs, two arginine fingers, and two sensor motifs distributed throughout the polypeptide chain of PLRV capsid protein (CP). The composition and arrangement of the ATP binding and hydrolysis domain of PLRV CP is unique and rarely reported. The discovery of the system sheds new light on the mechanism of viral genome packaging, regulation of viral assembly process, and evolution of plant viruses. Here, we used the RNAi approach to suppress CP gene expression, which in turn prevented PLRV genome packaging and assembly in Solanum tuberosum cv. Khufri Ashoka. Potato plants agroinfiltrated with siRNA constructs against the ATPase domain of CP exhibited no rolling symptoms upon PLRV infection, indicating that the silencing of CP gene expression is an efficient method for generating PLRV-resistant potato plants. Moreover, our findings provide a robust approach to generate PLRV-resistant potato plants, which can be further extended to other species. Finally, we propose a new mechanism of genome packaging and assembly in plant viruses.

molecular biology↗

bioRxiv2020

Cloning and In silico characterization of Heat shock factor (Hsf2) from Wheat (Triticum aestivum L.)

A gene that encodes for Heat Shock Factor (Hsf) was characterized and designated as TaHsf2 (Gen Bank ID: KP063542) from wheat. The genomic sequence was found to be 1551bp long with open reading frame of length1123bp. The amino acid sequence so concluded showed to have HSF domain having high degree of similarity (homology) with other HSF coding gene of related species. We have reported in-silico three-dimensional model of TaHsf2 and evaluation of the predicted model, analysed with various tools. The sudden climatic variations over the years especially elevation in temperature has adversely affected the growth and productivity of winter wheat (Triticum aestivum L.). A very less number of HSFs is being reported and characterized in wheat and the data so available for wheat calls for investigation and characterization of more HSPs coding HSFs. In our present study we have cloned one of the novel HSFs and have characterized it through in silico tools.

molecular biology↗