Ontology highlight
ABSTRACT:
PROVIDER: PRJNA923701 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23078411_subreads.fastq.gz | Fastqsanger.gz | |||
| SRR23078412_1.fastq.gz | Fastqsanger.gz | |||
| SRR23078412_2.fastq.gz | Fastqsanger.gz | |||
| SRR23078413_1.fastq.gz | Fastqsanger.gz | |||
| SRR23078413_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 11 |
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Project description:Dihydrofolate reductase activity is essential for the maintenance of One Carbon Metabolism, as it provides the pathway with tetrahydrofolate (the biologically active form of folate). Most of this cellular activity is due to DHFR. Its paralogue DHFR2 was thought to be responsible for mitochondrial dihydrofolate activity based on recombinant versions of the enzyme. However, the function of the endogenous gene/protein has yet to be assessed. This study aimed at investigating the effects of DHFR2 gene loss in HepG2 cells to help identify its function. Furthermore, the expression profile of the DHFR knockdown was interrogated to assess whether DHFR lowered expression has an impact on DHFR2.
2024-02-01 | E-MTAB-12958 | biostudies-arrayexpress
Project description:Investigation of whole genome gene expression level changes in Mycobacterium tuberculosis treated with the DHFR inhibitor WR99210, compared to untreated cells. The antimycobacterial properties of WR99210 are further described in Gerum, A., Ulmer, J., Jacobus, D., Jensen, N., Sherman, D., and C. Sibley. 2002. Novel Saccharomyces cerevisiae screen identifies WR99210 analogues that inhibit Mycobacterium tuberculosis dihydrofolate reductase. Antimicrob Agents Chemother 46(11):3362-3369 [PMID:12384337]
2012-09-18 | GSE40917 | GEO
Project description:RNA fragmentation and bisulfite conversion were performed. In brief, 200 ng of mRNAs along with 1 ng in vitro transcribed mouse dihydrofolate reductase (Dhfr) spike-in RNA were used. The bisulfite treated samples were desalted with Nanoseq with 3K omega 500/pk centrifugal devices (PALL). Sequencing was performed on an Illumina HiSeq X-Ten sequencing system. The m5C sites were called using meRanCall from meRanTK (FDR < 0.01). The differential m5C sites were detected
2019-07-02 | GSE133623 | GEO
Project description:Dihydrofolate reductase (DHFR) is a prominent molecular target in antitumor, antibacterial and antiprotozoan chemotherapies. Our in silico amino acid sequence and 3D structure analyses revealed the presence of several putative CK2 phosphorylation sites. Indeed, CK2α subunit phosphorylated DHFR in vitro. In order to identify phosphorylation site we used site-directed mutagenesis to obtain several DHFR mutants with predicted CK2-phosphorylable serine or threonine residues substituted with alanines. All enzyme forms were subjected to in vitro phosphorylation by CK2α subunit. The results pointed to serine 168. Mass spectrometry analyses revealed the presence of additional phosphoserine 145. Phosphorylation by CK2α of S145A mutant and lack of phosphorylation of S145A/S168A double mutant may indicate that S145 phosphorylation may occur only when serine 168 is already phosphorylated. The effect of these and other mutations on enzyme catalytic activity was also investigated.
2019-04-15 | PXD011853 | Pride
Project description:The relationship between sequence variation and phenotype is poorly understood. Here, we use metabolomic analysis to elucidate the molecular mechanism underlying the filamentous phenotype of E. coli strains that carry destabilizing mutations in dihydrofolate reductase (DHFR). We find that partial loss of DHFR activity causes reversible filamentation despite SOS response indicative of DNA damage, in contrast to thymineless death (TLD) achieved by complete inhibition of DHFR activity by high concentrations of antibiotic trimethoprim. This phenotype is triggered by a disproportionate drop in intracellular dTTP, which could not be explained by drop in dTMP based on the Michaelis-Menten-like in vitro activity curve of thymidylate kinase (Tmk), a downstream enzyme that phosphorylates dTMP to dTDP. Instead, we show that a highly cooperative (Hill coefficient 2.5) in vivo activity of Tmk is the cause of suboptimal dTTP levels. dTMP supplementation rescues filamentation and restores in vivo Tmk kinetics to Michaelis-Menten. Overall, this study highlights the important role of cellular environment in sculpting enzymatic kinetics with system-level implications for bacterial phenotype.
2021-06-30 | MTBLS2795 | MetaboLights
Project description:Investigation of whole genome gene expression level changes in Mycobacterium tuberculosis treated with the DHFR inhibitor WR99210, compared to untreated cells. The antimycobacterial properties of WR99210 are further described in Gerum, A., Ulmer, J., Jacobus, D., Jensen, N., Sherman, D., and C. Sibley. 2002. Novel Saccharomyces cerevisiae screen identifies WR99210 analogues that inhibit Mycobacterium tuberculosis dihydrofolate reductase. Antimicrob Agents Chemother 46(11):3362-3369 [PMID:12384337] A nine chip experiment in which total RNA was collected from H37Rv after treatment with 100 uM WR99210 for 0, 4, and 24 hours. Three separate cultures/biological replicates were interrogated for both treated and untreated cultures. Labeled cDNA was hybridized to NimbleGen spotted oligo tiling arrays covering both strands of the M. tuberculosis genome at ~200 bp intervals between 60-mer probes.
2012-09-18 | E-GEOD-40917 | biostudies-arrayexpress
Project description:We present PIGEON-FEATHER, a method for calculating free energies of opening (∆Gop) at single- or near-single-amino acid resolution for protein ensembles of all sizes from hydrogen exchange/mass spectrometry (HX/MS) data. PIGEON-FEATHER disambiguates and reconstructs all experimentally measured isotopic mass envelopes using a Bayesian Monte Carlo sampling approach. We applied PIGEON-FEATHER to reveal how E. coli and human dihydrofolate reductase (ecDHFR, hDHFR) have evolved distinct conformational ensembles tuned to their catalytic cycles. We showed how two competitive inhibitors of ecDHFR arrest its ensemble in different ways, only one of which is compatible with vertebrate DHFR orthologs. Finally, we uncovered how the lac repressor (LacI) ensemble responds to binding its inducer molecule and operator DNA to regulate transcriptional activation.
2024-11-05 | PXD057539 | Pride
Project description:We present PIGEON-FEATHER, a method for calculating free energies of opening (∆Gop) at single- or near-single-amino acid resolution for protein ensembles of all sizes from hydrogen exchange/mass spectrometry (HX/MS) data. PIGEON-FEATHER disambiguates and reconstructs all experimentally measured isotopic mass envelopes using a Bayesian Monte Carlo sampling approach. We applied PIGEON-FEATHER to reveal how E. coli and human dihydrofolate reductase (ecDHFR, hDHFR) have evolved distinct conformational ensembles tuned to their catalytic cycles. We showed how two competitive inhibitors of ecDHFR arrest its ensemble in different ways, only one of which is compatible with vertebrate DHFR orthologs. Finally, we uncovered how the lac repressor (LacI) ensemble responds to binding its inducer molecule and operator DNA to regulate transcriptional activation.
2024-08-06 | PXD054550 | Pride
Project description:Somatic rearrangements of transcription factors are common abnormalities in the acute leukemias. With rare exception, however, the resultant protein products have remained largely intractable as pharmacologic targets. One example is AML1-ETO, the most common translocation reported in acute myeloid leukemia (AML). To identify AML1-ETO modulators, we screened a small molecule library using a chemical genomic approach. Gene expression signatures were used as surrogates for the expression versus loss of the translocation in AML1-ETO-expressing cells. The top classes of compounds that scored in this screen were corticosteroids and dihydrofolate reductase (DHFR) inhibitors. In addition to modulating the AML1-ETO signature, both classes induced evidence of differentiation, dramatically inhibited cell viability, and ultimately induced apoptosis via on-target activity. Furthermore, AML1-ETO-expressing cell lines were exquisitely sensitive to the effects of corticosteroids on cellular viability compared with nonexpressers. The corticosteroids diminished AML1-ETO protein in AML cells in a proteasome- and glucocorticoid receptor-dependent manner. Moreover, these molecule classes demonstrated synergy in combination with standard AML chemotherapy agents and activity in an orthotopic model of AML1-ETO-positive AML. This work suggests a role for DHFR inhibitors and corticosteroids in treating patients with AML1-ETO-positive disease.
2016-12-08 | GSE91002 | GEO
Project description:The main cause of death in medulloblastoma is recurrence associated with leptomeningeal dissemination. Although the molecular basis of medulloblastoma has received considerable attention over the past decade, the role of microRNAs (miRNAs) in the acquisition of metastatic phenotype remains poorly understood. This study aimed to identify miRNA involved in leptomeningeal dissemination and to elucidate its target mechanisms. We analyzed miRNA expression profiles of 29 medulloblastomas according to the presence of cerebrospinal fluid (CSF) seeding. The differential expressed miRNAs (DEmiRNAs) were validated on 29 medulloblastoma tissues and three medulloblastoma cells. The biological function of the selected miRNA was evaluated using in vitro studies. A total of 12 DEmiRNAs were identified including miRNA-192 in medulloblastoma with seeding. The reduced expression of miRNA-192 was confirmed in tumor seeding group and the medulloblastoma cells. Overexpression of miRNA-192 inhibited cellular proliferation targeting dihydrofolate reductase (DHFR). MiRNA-192 decreased cellular anchoring via repression of integrin subunits (αV, β1, and β3) and CD47. Medulloblastoma with seeding showed specific DEmiRNAs compared with those without seeding. MicroRNA-192 suppresses leptomeningeal dissemination of medulloblastoma through modulating cell proliferation and anchoring ability. leptomeningeal dissemination in 29 pediatric medulloblastoma patients
2015-12-31 | E-GEOD-66968 | biostudies-arrayexpress