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Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) and NOD2 are cytosolic pattern recognition receptors playing pivotal roles in innate immune signaling. NOD1 and NOD2 recognize bacterial peptidoglycan derivatives iE-DAP and MDP, respectively and undergoes conformational alternation and ATP-dependent self-oligomerization of NACHT domain followed by downstream signaling. Lack of structural adequacy of NACHT domain confines our understanding about the NOD-mediated signaling mechanism. Here, we predicted the structure of NACHT domain of both NOD1 and NOD2 from model organism zebrafish (Danio rerio) using computational methods. Our study highlighted the differential ATP binding modes in NOD1 and NOD2. In NOD1, γ-phosphate of ATP faced toward the central nucleotide binding cavity like NLRC4, whereas in NOD2 the cavity was occupied by adenine moiety. The conserved 'Lysine' at Walker A formed hydrogen bonds (H-bonds) and Aspartic acid (Walker B) formed electrostatic interaction with ATP. At Sensor 1, Arg328 of NOD1 exhibited an H-bond with ATP, whereas corresponding Arg404 of NOD2 did not. 'Proline' of GxP motif (Pro386 of NOD1 and Pro464 of NOD2) interacted with adenine moiety and His511 at Sensor 2 of NOD1 interacted with γ-phosphate group of ATP. In contrast, His579 of NOD2 interacted with the adenine moiety having a relatively inverted orientation. Our findings are well supplemented with the molecular interaction of ATP with NLRC4, and consistent with mutagenesis data reported for human, which indicates evolutionary shared NOD signaling mechanism. Together, this study provides novel insights into ATP binding mechanism, and highlights the differential ATP binding modes in zebrafish NOD1 and NOD2.

Bioinformatics tools are recently used in various sectors of biology. Many questions regarding Neurodevelopmental disorder which arises as a major health issue recently can be solved by using various bioinformatics databases. Schizophrenia is such a mental disorder which is now arises as a major threat in young age people because it is mostly seen in case of people during their late adolescence or early adulthood period. Databases like DISGENET, GWAS, PHARMGKB, and DRUGBANK have huge repository of genes associated with schizophrenia. We found a lot of genes are being associated with schizophrenia, but approximately 200 genes are found to be present in any of these databases. After further screening out process 20 genes are found to be highly associated with each other and are also a common genes in many other diseases also. It is also found that they all are serves as a common targeting gene in many antipsychotic drugs. After analysis of various biological properties, molecular function it is found that these 20 genes are mostly involved in biological regulation process and are having receptor activity. They are belonging mainly to receptor protein class. Among these 20 genes CYP2C9, CYP3A4, DRD2, HTR1A, HTR2A are shown to be a main targeting genes of most of the antipsychotic drugs and are associated with more than 40% diseases. The basic findings of the present study enumerated that a suitable combined drug can be design by targeting these genes which can be used for the better treatment of schizophrenia.

Wheat ( Triticum aestivum L.), a vital cereal crop, provides over 20% of the total calories and protein in the human diet. However, Fusarium graminearum , the pathogen responsible for Fusarium head blight (FHB), poses a significant threat to wheat production by contaminating grains with harmful mycotoxins. Although Fusarium head blight is currently a minor disease in India, it has the potential to cause substantial yield and quality losses, especially if rain occurs during mid-anthesis. Epigenetic mechanisms, including DNA methylation and sRNA accumulation, are crucial in regulating gene expression and enabling plants to adapt to environmental stresses. Previous studies investigating wheat's response to F . graminearum through transcriptome analysis of lines differing in 2DL FHB resistance QTLs did not fully explore the role of methylation-related genes. To address this gap, we re-analyzed RNA-Seq data to uncover the response of methylation-related genes to pathogen infection. Our analysis revealed that 16 methylation-related genes were down-regulated in the susceptible line 2–2890, with Gene Ontology (GO) analysis linking these genes to L-methionine salvage from methylthioadenosine (GO:0019509), S-adenosylmethionine metabolism (GO:0033353), and steroid biosynthesis (GO:0006694) ( p -value = 0.001). Co-expression analysis identified a negative correlation (−0.82) between methionine S-methyl-transferase (MSM; TraesCS1A02G013800) and 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR; TraesCS5A02G269300). HMGCR also showed negative correlations (−1.00) with genes encoding pathogenesis-related, detoxification proteins, and xylanase inhibitors, with GO associating these genes with methionine S-methyl transferase activity ( p -value = 0.001). In pathogen-inoculated samples, the elevated expression of HMGCR (Log2 3.25–4.00) and the suppression of MSM (Log2 1.25–3.25) suggest a dual role in stress response and susceptibility, potentially linked to disrupted DNA methylation and isoprenoid biosynthesis pathways. Furthermore, 43 genes down-regulated by miR9678 were associated with biotic stimulus responses and glucan endo-1,4-beta-glucanase activity, highlighting the complex regulatory networks involved in wheat's defense against F . graminearum . This study reveals the roles of methylation-related genes in susceptible wheat lines 2–2890, providing new insights into their potential impact on pathogen response and plant susceptibility.

Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) and NOD2 are cytosolic pattern recognition receptors playing pivotal roles in innate immune signaling. NOD1 and NOD2 recognize bacterial peptidoglycan derivatives iE-DAP and MDP, respectively and undergoes conformational alternation and ATP-dependent self-oligomerization of NACHT domain followed by downstream signaling. Lack of structural adequacy of NACHT domain confines our understanding about the NOD-mediated signaling mechanism. Here, we predicted the structure of NACHT domain of both NOD1 and NOD2 from model organism zebrafish (Danio rerio) using computational methods. Our study highlighted the differential ATP binding modes in NOD1 and NOD2. In NOD1, gamma -phosphate of ATP faced toward the central nucleotide binding cavity like NLRC4, whereas in NOD2 the cavity was occupied by adenine moiety. The conserved 'Lysine' at Walker A formed hydrogen bonds (H-bonds) and Aspartic acid (Walker B) formed electrostatic interaction with ATP. At Sensor 1, Arg328 of NOD1 exhibited an H-bond with ATP, whereas corresponding Arg404 of NOD2 did not. 'Proline' of GxP motif (Pro386 of NOD1 and Pro464 of NOD2) interacted with adenine moiety and His511 at Sensor 2 of NOD1 interacted with gamma -phosphate group of ATP. In contrast, His579 of NOD2 interacted with the adenine moiety having a relatively inverted orientation. Our findings are well supplemented with the molecular interaction of ATP with NLRC4, and consistent with mutagenesis data reported for human, which indicates evolutionary shared NOD signaling mechanism. Together, this study provides novel insights into ATP binding mechanism, and highlights the differential ATP binding modes in zebrafish NOD1 and NOD2.