methyltranferase

A series of S -adenosyl-L-homosysteine (SAH) analogs, with modification in the base and sugar moiety, have been designed, synthesized and screened as nsp14 and PLpro inhibitors of severe acute respiratory syndrome corona virus (SARS-CoV-2). The outcomes of ADMET (Adsorption, Distribution, Metabolism, Excretion, and Toxicity) studies demonstrated that the physicochemical properties of all analogs were permissible for development of these SAH analogs as antiviral agents. All molecules were screened against different SARS-CoV-2 targets using molecular docking...

DNA methylation plays an important role in epigenetic modification. DNA methyltransferase (DNMT) is essential in the DNA methylation process, and its abnormal expression is closely related to cancer. In this study, we propose a novel biosensor platform (DS-GlaI-EXPAR) that combines hemi-methylated double-stranded DNA (dsDNA) as the substrate for DNMT1 with GlaI-assisted isothermal exponential amplification reaction (EXPAR) for rapid, simple, and sensitive detection of DNMT1 activity. The hemi-methylated dsDNA is fully methylated by DNMT1, and GlaI recognizes and cleaves the fully methylated sequence, generating terminal fragments that trigger EXPAR for efficient signal amplification...

Putative methyltranferase LaeA and LaeA-like proteins, conserved in many filamentous fungi, regulate fungal growth, development, virulence, the biosynthesis of secondary metabolites, and the production of cellulolytic enzymes. Penicillium oxaliucm is a typical fungus that produces cellulolytic enzymes. In this study, we reported the biological function of eight putative methyltransferases (PoMtr23C/D/E/F/G/H and PoMtr25A/B) containing a methyltransf_23 or methyltransf_25 domain, with a focus on their roles in the production of cellulolytic enzymes...

BACKGROUND: Post-translational modifications play key roles in various biological processes. Protein arginine methyltransferases (PRMTs) transfer the methyl group to specific arginine residues. Both PRMT1 and PRMT6 have emerges as crucial factors in the development and progression of multiple cancer types. We posit that PRMT1 and PRMT6 might interplay directly or in-directly in multiple ways accounting for shared disease phenotypes. AIM: To investigate the mechanism of the interaction between PRMT1 and PRMT6...

Consumption of a Western diet is an important risk factor for several chronic diseases including nonalcoholic fatty liver disease (NAFLD), but its effect on the xenobiotic metabolizing enzyme activities in the liver has been studied incompletely. In this study, male LDLr-/- ApoB100/100 mice were fed with Western diet (WD) or a standard diet for five months to reveal the effects on drug metabolism such as cytochrome P450 (CYP) oxidation and conjugation activities in the liver. Hepatic steatosis, lobular inflammation, and early fibrosis were observed in WD fed mice, but not in chow diet control mice...

High temperature stress (HTS), with growth and development impairment, is one of the most important abiotic stresses frequently encountered by plants, in particular solanacaes such as pepper, that mainly distribute in tropical and subtropical regions. Plants activate thermotolerance to cope with this stress; however, the underlying mechanism is currently not fully understood. SWC4, a shared component of SWR1- and NuA4 complexes implicated in chromatin remodeling, was previously found to be involved in the regulation of pepper thermotolerance, but the underlying mechanism remains poorly understood...

Aspergillus fumigatus causes a range of human and animal diseases collectively known as aspergillosis. A. fumigatus possesses and expresses a range of genetic determinants of virulence, which facilitate colonisation and disease progression, including the secretion of mycotoxins. Gliotoxin (GT) is the best studied A. fumigatus mycotoxin with a wide range of known toxic effects that impair human immune cell function. GT is also highly toxic to A. fumigatus and this fungus has evolved self-protection mechanisms that include (i) the GT efflux pump GliA, (ii) the GT neutralising enzyme GliT, and (iii) the negative regulation of GT biosynthesis by the bis-thiomethyltransferase GtmA...

BACKGROUND AND PURPOSE: Development of pulmonary fibrosis is associated with altered DNA methylation modifications of fibrogenic gene expression. However, their causal relationships and the underlying mechanisms remain unclear. This study investigates the critical role of DNA methylation aberration-associated suppression of peroxisome proliferator-activated receptor-γ (PPARγ) in pulmonary fibrosis. EXPERIMENTAL APPROACH: Expression of PPARγ and bioactive DNA methyltransferases (DNMTs) and PPARγ promoter methylation status were examined in fibrotic lungs of idiopathic pulmonary fibrosis (IPF) patients and bleomycin (Blm)-treated mice...

Different classes of non-coding RNA (ncRNA) influence the organization of chromatin. Imprinted gene domains constitute a paradigm for exploring functional long ncRNAs (lncRNAs). Almost all express an lncRNA in a parent-of-origin dependent manner. The mono-allelic expression of these lncRNAs represses close by and distant protein-coding genes, through diverse mechanisms. Some control genes on other chromosomes as well. Interestingly, several imprinted chromosomal domains show a developmentally regulated, chromatin-based mechanism of imprinting with apparent similarities to X-chromosome inactivation...

Hypermonins A-D ( 1 - 4 ), four rearranged nor-polycyclic polyprenylated acylphloroglucinols (PPAPs) with unprecedented skeletons, together with two new biosynthesis related PPAPs ( 5 and 6 ) were isolated and identified from the flowers of Hypericum monogynum . Hypermoins A-D represented the first examples of highly modified norPPAPs characterized by a rare 7/6/6/5-tetracyclic system. From the biogenic synthesis pathway analysis, all isolates shared the same biosynthetic intermediate, and the addition of two methyls or one methyl to this intermediate through methyltranferase could generate different types of PPAPs ( 1 - 7 )...

The novel Coronavirus disease 2019 (COVID-19) is potentially fatal and caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Due to the unavailability of any proven treatment or vaccination, the outbreak of COVID-19 is wreaking havoc worldwide. Hence, there is an urgent need for therapeutics targeting SARS-CoV-2. Since, botanicals are an important resource for several efficacious antiviral agents, natural compounds gaining significant attention for COVID-19 treatment. In the present study, methyltranferase (MTase) of the SARS-CoV-2 is targeted using computational approach...

INTRODUCTION: Radiotherapy-induced glioblastomas (RIGB) are a well-known late and rare complication of brain irradiation. Yet the clinical, radiological and molecular characteristics of these tumors are not well characterized. METHODS: This was a retrospective multicentre study that analysed adult patients with newly diagnosed glioblastoma over a 10-year period. Patients with RIGB were identified according to Cahan's criteria for radiation-induced tumors. A case-control analysis was performed to compare known prognostic factors for overall survival (OS) with an independent cohort of IDH-1 wildtype de novo glioblastomas treated with standard temozolomide chemoradiotherapy...

Creatine kinase (CK) is considered the main phosphotransfer system in the heart, important for overcoming diffusion restrictions and regulating mitochondrial respiration. It is substrate limited in creatine-deficient mice lacking l-arginine:glycine amidinotransferase (AGAT) or guanidinoacetate N -methyltranferase (GAMT). Our aim was to determine the expression, activity, and mitochondrial coupling of hexokinase (HK) and adenylate kinase (AK), as these represent alternative energy transfer systems. In permeabilized cardiomyocytes, we assessed how much endogenous ADP generated by HK, AK, or CK stimulated mitochondrial respiration and how much was channeled to mitochondria...

BACKGROUND: The presence of 16S rRNA methyltranferases (16S-RMTases) in carbapenemase-producing Enterobacterales (CPE) is a major concern because it inactivates all clinical use of aminoglycosides, including plazomicin. The aim of this study is to investigate the prevalence of 16S-RMTases in CPE nonsusceptible to plazomicin collected in different Brazilian hospitals. METHODS: All isolates with plazomicin MIC ≥ 4 µg/mL (n = 67) were screened for the presence of 16S-RMTases by sequencing...

Objective: To investigate the effect and mechanism of Polyphyllin Ⅱ on the proliferation, invasion and chemosensitivity of glioma cells. Method: CCK-8 cell proliferation assays and Transwell assays were employed to determine the effect of Polyphyllin Ⅱ on the proliferation and invasion of glioma cells (T98G and LN18), respectively. The expression of E-cadherin, Snail and O6-methylguanine DNA methyltranferase (MGMT) were quantified by Western blot analysis. Results: Polyphyllin Ⅱ could inhibit the proliferation of glioma cells in a time- and does-dependent manner...

Putative methyltranferase LaeA and LaeA-like proteins, which are conserved in many filamentous fungi, regulate the sporogenesis and biosynthesis of secondary metabolites. In this study, we reported the biological function of a LaeA-like methyltransferase, Penicillium oxalicum Mtr23B, which contains a methyltransf_23 domain and an S-adenosylmethionine binding domain, in controlling spore pigment formation and in the expression of secondary metabolic gene cluster and glycoside hydrolase genes. Additionally, we compared Mtr23B and LaeA, and determined their similarities and differences in terms of their roles in regulating the above biological processes...

Epigenetic modifications of histones have crucial roles in various types of cancers. The aberrant trimethylation of histone H4 at lysine 20 (H4K20) has been implicated in carcinogenesis. At present, the status of trimethylation at H4k20 (H4K20me3) in osteosarcoma (OS), the predominant bone cancer in humans, is unknown. In the present study, a genome-wide decrease was observed in H4K20me3 levels in OS tissues and cell lines. Reduced levels of lysine methyltransferase 5C (SUV420H2), the histone methyltranferase responsible for modification of H4K20me3, was also observed in OS cells with the associated loss of H4K20me3...

3-Isobutyl-2-methoxypyrazine (IBMP) is an important odor compound that revives unripe grapes or poor-quality wine. The biosynthesis of IBMP in grape berries is under the catalysis of Vitis vinifera O-methyltranferase 3 (VvOMT3). The homologous verification in this paper was carried out with the transient overexpression technique. The results showed that both the expression levels of the VvOMT3 gene and the IBMP concentration in 'Red globe' grapes increased significantly, which suggested that VvOMT3 could function in the biosynthesis of IBMP...

Background: Several lines of research have suggested that the 472G > A (Val158Met) polymorphism at Catechol-O-methyltranferase (COMT) gene is implicated in the pathophysiology of FMS. Here, we have evaluated the association of COMT 472G > A polymorphism with risk of FMS. Methods: In this study 250 patients with FMS and 250 healthy controls were evaluated for COMT 472G > A polymorphism by RFLP-PCR assay. Results: There were no significant differences in the allele and genotype frequencies of COMT 472G > A polymorphism between FMS cases and healthy controls...

BACKGROUND: Avian hepatitis E virus (aHEV) has been associated with hepatitis-splenomegaly syndrome (HSS) in chickens along with asymptomatic subclinical infection in many cases. So far, four genotypes have been described, which cause infection in chickens, specifically in broiler breeders and layer chickens. In the present study, we isolated and identified two novel aHEV strains from the bile of layer chickens in Pakistan evincing clinical symptoms related to HSS. METHODOLOGY: Histology of liver and spleen tissues was carried out to observe histopathological changes in these tissues...