Dataset on double mutation in PGIP of Glycine max improves defense to PG of Sclerotinia sclerotiorum.

The cell wall of the Glycine max altered by the polygalacturonases (PGs) secreted by the fungus Sclerotinia sclerotiorum, causes disease and quality losses. In soybeans, a resistance protein called polygalacturonases-inhibiting proteins (PGIPs) binds to the PG to block fungal infection. The active site residues of PGIP3, VAL170 and GLN242 are mutated naturally by various amino acids in different types of PGIPs. Therefore, the mutation of VAL170 to GLY is ineffective but the GLN242 amino acid mutation by LYS significantly alters the structure and is crucial for interacting with the PG protein. Docking and Molecular Dynamics simulation provide a comprehensive evaluation of the interactions between gmPGIP and ssPG. By elucidating the structural basis of the interaction between gmPGIP and ssPG, this investigation lays a foundation for the development of targeted strategies in-order to enhance soybean resistance against Sclerotinia sclerotiorum. By leveraging this knowledge, researchers can potentially engineer soybean varieties with improved resistance to the fungus, thereby reducing disease incidence and improving crop yields.

Metagenomics analysis of water samples collected from the Yamuna River of Agra city, India.

Yamuna River water in Agra city of India is contaminated with toxic pollutants, including heavy metals that cause damage to the environment and human health. At present, the direct use of river water for drinking purposes and household activities lead to the direct exposure of society to the contaminants. In this study, Yamuna River water samples were collected from three different sites in Agra city during the monsoon, summer, and winter seasons. The physico-chemical parameters were estimated along with heavy metals. In physico-chemical parameter, the values found were mostly above the permissible limits. The results water samples contain high levels of cadmium, chromium, lead, and nickel above the desirable levels in most cases. The metagenomic analysis revealed that Proteobacteria, Bacteroidetes, Verrucomicrobia, Actinobacteria, and Planctobacteria were the most abundant phyla with a relative abundance of 61%, 9.34%, 5.23%, 4.64%, and 4.3%, respectively. The Comamonadaceae, the most abundant family consists of the genera involved in hydrogen oxidation, iron reduction, degraders of polycyclic aromatic hydrocarbons, and fermentation. The presence of Pseudomonas, Nitrosomonas sp., Thauera humireducens and Dechloromonas denitrificans (decomposition of sewage and organic matter) and Pseudomonas aeruginosa indicates the presence of heavy metal degrading bacteria in water sample. Functional prediction showed the presence of genes responsible for different metabolic pathways that could help developing new bioremediation strategies. The study concludes the status of water contamination, the presence of complex microbial community and suggests the futuristic use and their role in bioremediation.

In silico mutation of aromatic with aliphatic amino acid residues in Clostridium perfringens epsilon toxin (ETX) reduces its binding efficiency to Caprine Myelin and lymphocyte (MAL) protein receptors.

Enterotoxaemia (ET) is a severe disease that affects domestic ruminants, including sheep and goats, and is caused by Clostridium perfringens type B and D strains. The disease is characterized by the production of Epsilon toxin (ETX), which has a significant impact on the farming industry due to its high lethality. The binding of ETX to the host cell receptor is crucial, but still poorly understood. Therefore, the structural features of goat Myelin and lymphocytic (MAL) protein were investigated and defined in this study. We induced the mutations in aromatic amino acid residues of ETX and substituted them with aliphatic residues at domains I and II. Subsequently, protein-protein interactions (PPI) were performed between ETX (wild)-MAL and ETX (mutated)-MAL protein predicting the domain sites of ETX structure. Further, molecular dynamics (MD) simulation studies were performed for both complexes to investigate the dynamic behavior of the proteins. The binding efficiency between 'ETX (wild)-MAL protein' and 'ETX (mutated)-MAL protein complex' interactions were compared and showed that the former had stronger interactions and binding efficiency due to the higher stability of the complex. The MD analysis showed destabilization and higher fluctuations in the PPI of the mutated heterodimeric ETX-MAL complex which is otherwise essential for its functional conformation. Such kind of interactions with mutated functional domains of ligands provided much-needed clarity in understanding the pre-pore complex formation of epsilon toxin with the MAL protein receptor of goats. The findings from this study would provide an impetus for designing a novel vaccine for Enterotoxaemia in goats.Communicated by Ramaswamy H. Sarma.

Unraveling the Aurora kinase A and Epstein-Barr nuclear antigen 1 axis in Epstein Barr virus associated gastric cancer.

Aurora kinase A (AURKA) is one of the crucial cell cycle regulators associated with gastric cancer. Here, we explored Epstein Barr Virus-induced gastric cancer progression through EBV protein EBNA1 with AURKA. We found that EBV infection enhanced cell proliferation and migration of AGS cells and upregulation of AURKA levels. AURKA knockdown markedly reduced the proliferation and migration of the AGS cells even with EBV infection. Moreover, MD-simulation data deciphered the probable connection between EBNA1 and AURKA. The in-vitro analysis through the transcript and protein expression showed that AURKA knockdown reduces the expression of EBNA1. Moreover, EBNA1 alone can enhance AURKA protein expression in AGS cells. Co-immunoprecipitation and NMR analysis between AURKA and EBNA1 depicts the interaction between two proteins. In addition, AURKA knockdown promotes apoptosis in EBV-infected AGS cells through cleavage of Caspase-3, -9, and PARP1. This study demonstrates that EBV oncogenic modulators EBNA1 possibly modulate AURKA in EBV-mediated gastric cancer progression.

A Drug Repurposing Approach to Identify Therapeutics by Screening Pathogen Box Exploiting SARS-CoV-2 Main Protease.

Coronavirus disease-19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2) and is responsible for a higher degree of morbidity and mortality worldwide. There is a smaller number of approved therapeutics available to target the SARS-CoV-2 virus, and the virus is evolving at a fast pace. So, there is a continuous need for new therapeutics to combat COVID-19. The main protease (Mpro ) enzyme of SARS-CoV-2 is essential for replication and transcription of the viral genome, thus could be a potent target for the treatment of COVID-19. In the present study, we performed an in-silico screening analysis of 400 diverse bioactive inhibitors with proven antibacterial and antiviral properties against Mpro drug target. Ten compounds showed a higher binding affinity for Mpro than the reference compound (N3), with desired physicochemical properties. Furthermore, in-depth docking and superimposition revealed that three compounds (MMV1782211, MMV1782220, and MMV1578574) are actively interacting with the catalytic domain of Mpro . In addition, the molecular dynamics simulation study showed a solid and stable interaction of MMV178221-Mpro complex compared to the other two molecules (MMV1782220, and MMV1578574). In line with this observation, MM/PBSA free energy calculation also demonstrated the highest binding free energy of -115.8 kJ/mol for MMV178221-Mpro compound. In conclusion, the present in silico analysis revealed MMV1782211 as a possible and potent molecule to target the Mpro and must be explored in vitro and in vivo to combat the COVID-19.

Novel Insights into Understanding the Molecular Dialogues between Bipolaroxin and the Gα and Gß Subunits of the Wheat Heterotrimeric G-Protein during Host-Pathogen Interaction.

Spot blotch disease of wheat, caused by the fungus Bipolaris sorokiniana (Sacc.) Shoem., produces several toxins which interact with the plants and thereby increase the blightening of the wheat leaves, and Bipolaroxin is one of them. There is an urgent need to decipher the molecular interaction between wheat and the toxin Bipolaroxin for in-depth understanding of host-pathogen interactions. In the present study, we have developed the three-dimensional structure of G-protein alpha subunit from Triticum aestivum. Molecular docking studies were performed using the active site of the modeled G-protein alpha and cryo-EM structure of beta subunit from T. aestivum and 'Bipolaroxin'. The study of protein-ligand interactions revealed that six H-bonds are mainly formed by Glu29, Ser30, Lys32, and Ala177 of G-alpha with Bipolaroxin. In the beta subunit, the residues of the core beta strand domain participate in the ligand interaction where Lys256, Phe306, and Leu352 formed seven H-bonds with the ligand Bipolaroxin. All-atoms molecular dynamics (MD) simulation studies were conducted for G-alpha and -beta subunit and Bipolaroxin complexes to explore the stability, conformational flexibility, and dynamic behavior of the complex system. In planta studies clearly indicated that application of Bipolaroxin significantly impacted the physio-biochemical pathways in wheat and led to the blightening of leaves in susceptible cultivars as compared to resistant ones. Further, it interacted with the Gα and Gß subunits of G-protein, phenylpropanoid, and MAPK pathways, which is clearly supported by the qPCR results. This study gives deeper insights into understanding the molecular dialogues between Bipolaroxin and the Gα and Gß subunits of the wheat heterotrimeric G-protein during host-pathogen interaction.

Biocomputational Assessment of Natural Compounds as a Potent Inhibitor to Quorum Sensors in Ralstonia solanacearum.

Ralstonia solanacearum is among the most damaging bacterial phytopathogens with a wide number of hosts and a broad geographic distribution worldwide. The pathway of phenotype conversion (Phc) is operated by quorum-sensing signals and modulated through the (R)-methyl 3-hydroxypalmitate (3-OH PAME) in R. solanacearum. However, the molecular structures of the Phc pathway components are not yet established, and the structural consequences of 3-OH PAME on quorum sensing are not well studied. In this study, 3D structures of quorum-sensing proteins of the Phc pathway (PhcA and PhcR) were computationally modeled, followed by the virtual screening of the natural compounds library against the predicted active site residues of PhcA and PhcR proteins that could be employed in limiting signaling through 3-OH PAME. Two of the best scoring common ligands ZINC000014762512 and ZINC000011865192 for PhcA and PhcR were further analyzed utilizing orbital energies such as HOMO and LUMO, followed by molecular dynamics simulations of the complexes for 100 ns to determine the ligands binding stability. The findings indicate that ZINC000014762512 and ZINC000011865192 may be capable of inhibiting both PhcA and PhcR. We believe that, after further validation, these compounds may have the potential to disrupt bacterial quorum sensing and thus control this devastating phytopathogenic bacterial pathogen.

Delineation of molecular interactions of plant growth promoting bacteria induced ß-1,3-glucanases and guanosine triphosphate ligand for antifungal response in rice: a molecular dynamics approach.

BACKGROUND: The plant growth is influenced by multiple interactions with biotic (microbial) and abiotic components in their surroundings. These microbial interactions have both positive and negative effects on plant. Plant growth promoting bacterial (PGPR) interaction could result in positive growth under normal as well as in stress conditions. METHODS: Here, we have screened two PGPR's and determined their potential in induction of specific gene in host plant to overcome the adverse effect of biotic stress caused by Magnaporthe grisea, a fungal pathogen that cause blast in rice. We demonstrated the glucanase protein mode of action by performing comparative modeling and molecular docking of guanosine triphosphate (GTP) ligand with the protein. Besides, molecular dynamic simulations have been performed to understand the behavior of the glucanase-GTP complex. RESULTS: The results clearly showed that selected PGPR was better able to induce modification in host plant at morphological, biochemical, physiological and molecular level by activating the expression of ß-1,3-glucanases gene in infected host plant. The docking results indicated that Tyr75, Arg256, Gly258, and Ser223 of glucanase formed four crucial hydrogen bonds with the GTP, while, only Val220 found to form hydrophobic contact with ligand. CONCLUSIONS: The PGPR able to induce ß-1,3-glucanases gene in host plant upon pathogenic interaction and ß-1,3-glucanases form complex with GTP by hydrophilic interaction for induction of defense cascade for acquiring resistance against Magnaporthe grisea.

Season of birth is not associated with age at menarche in young adults from Central India.

OBJECTIVES: We aimed to test whether birth season is associated with age at menarche in the sub-tropical climate of Central India where temperature and photoperiod differences between seasons are very small. METHODS: Date of birth and age at menarche were collected for 330 female students of Central University, Sagar. The impact of birth month and birth season on age at menarche was analyzed using ANOVA and time-to-event analysis with the use of the Kaplan-Meier curve. RESULTS: ANOVA, Kaplan-Meier estimation and Cox Proportional Hazard did not show statistically significant differences in age at menarche according to birth month and birth season. CONCLUSIONS: Constant sun exposure during the whole year, related to a stable vitamin D amount and to equal access to fruits and vegetables, may translate into a lack of association between seasons and age at menarche.